Molecules


Each species needs a location tag (outside,membrane,cytoplasms,destroyed etc..)

EGF(EGFL,deg~F~T,loc~Ex~En)

EGF EGFL deg F T loc Ex En

HRG(EGFL,deg~F~T,loc~Ex~En)

HRG EGFL deg F T loc Ex En

EGFR(I_III,II,T669~O~P,Y992~O~P,Y1068~O~P,Y1086~O~P,Y1114~O~P,Y1148~O~P,Y1173~O~P,loc~M~En)

EGFR I_III II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En

ErbB2(II,Y1139~O~P,Y1196~O~P,Y1222~O~P,Y1248~O~P,loc~M~En)

ErbB2 II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En

ErbB3(I_III,II,Y1054~O~P,Y1197~O~P,Y1222~O~P,Y1260~O~P,Y1276~O~P,Y1289~O~P,Y1328~O~P,loc~M~En)

ErbB3 I_III II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M En

ErbB4(I_III,II,Y1056~O~P,Y1188~O~P,Y1242~O~P,loc~M~En)

ErbB4 I_III II Y1056 O P Y1188 O P Y1242 O P loc M En

p52Shc1(PTB,Y317~O~P,loc~C)

p52Shc1 PTB Y317 O P loc C

Grb2(SH2r,SH2s,cSH3,nSH3,loc~C)

Grb2 SH2r SH2s cSH3 nSH3 loc C

Sos1(PRS,REM,GEF,S1132~O~P,S1167~O~P,S1178~O~P,S1193~O~P,loc~C)

Sos1 PRS REM GEF S1132 O P S1167 O P S1178 O P S1193 O P loc C

S581 means S551, Y619 means Y627, Y657 means Y659

Gab1(PH,PRS1_PRS2,T312~O~P,S381~O~P,Y447~O~P,S454~O~P,Y472~O~P,T476~O~P,S581~O~P,S597~O~P,Y619~O~P,Y657~O~P,loc~C)

Gab1 PH PRS1_PRS2 T312 O P S381 O P Y447 O P S454 O P Y472 O P T476 O P S581 O P S597 O P Y619 O P Y657 O P loc C

PI3K(lipid_kinase,R_p85_nSH2_cSH2,G_p85_nSH2_cSH2,p110_RBD,loc~C)

PI3K lipid_kinase R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc C

PIP3(C3P,two~F~T,loc~M)

PIP3 C3P two F T loc M

PDK1(PH,STkinase,loc~C)

PDK1 PH STkinase loc C

Akt1(PH,STkinase,T308~O~P,S473~O~P,loc~C)

Akt1 PH STkinase T308 O P S473 O P loc C

KRas(GTPase,g~GDP~GTP,loc~M)

KRas GTPase g GDP GTP loc M

p120RasGAP(nSH2,GAP)

p120RasGAP nSH2 GAP

Raf1(RBD,STkinase,S29~O~P,S43~O~P,S259~O~P,S289~O~P,S296~O~P,S301~O~P,S338~O~P,Y341~O~P,S471~O~P,T491~O~P,S494~O~P,S642~O~P,loc~C)

Raf1 RBD STkinase S29 O P S43 O P S259 O P S289 O P S296 O P S301 O P S338 O P Y341 O P S471 O P T491 O P S494 O P S642 O P loc C

MEK1(delta,S218~O~P,S222~O~P,T292~O~P,loc~C)

MEK1 delta S218 O P S222 O P T292 O P loc C

ERK2(CD,STkinase,T185~O~P,Y187~O~P,loc~C)

ERK2 CD STkinase T185 O P Y187 O P loc C

Species

EGF(EGFL,deg~F,loc~Ex)

EGF EGFL deg F loc Ex

HRG(EGFL,deg~F,loc~Ex)

HRG EGFL deg F loc Ex

EGFR(I_III,II,T669~O,Y992~O,Y1068~O,Y1086~O,Y1114~O,Y1148~O,Y1173~O,loc~M)

EGFR I_III II T669 O Y992 O Y1068 O Y1086 O Y1114 O Y1148 O Y1173 O loc M

ErbB2(II,Y1139~O,Y1196~O,Y1222~O,Y1248~O,loc~M)

ErbB2 II Y1139 O Y1196 O Y1222 O Y1248 O loc M

ErbB3(I_III,II,Y1054~O,Y1197~O,Y1222~O,Y1260~O,Y1276~O,Y1289~O,Y1328~O,loc~M)

ErbB3 I_III II Y1054 O Y1197 O Y1222 O Y1260 O Y1276 O Y1289 O Y1328 O loc M

ErbB4(I_III,II,Y1056~O,Y1188~O,Y1242~O,loc~M)

ErbB4 I_III II Y1056 O Y1188 O Y1242 O loc M

p52Shc1(PTB,Y317~O,loc~C)

p52Shc1 PTB Y317 O loc C

Grb2(SH2r,SH2s,cSH3,nSH3,loc~C)

Grb2 SH2r SH2s cSH3 nSH3 loc C

Sos1(PRS,REM,GEF,S1132~O,S1167~O,S1178~O,S1193~O,loc~C)

Sos1 PRS REM GEF S1132 O S1167 O S1178 O S1193 O loc C

Gab1(PH,PRS1_PRS2,T312~O,S381~O,Y447~O,S454~O,Y472~O,T476~O,S581~O,S597~O,Y619~O,Y657~O,loc~C)

Gab1 PH PRS1_PRS2 T312 O S381 O Y447 O S454 O Y472 O T476 O S581 O S597 O Y619 O Y657 O loc C

PI3K(lipid_kinase,G_p85_nSH2_cSH2,R_p85_nSH2_cSH2,p110_RBD,loc~C)

PI3K lipid_kinase G_p85_nSH2_cSH2 R_p85_nSH2_cSH2 p110_RBD loc C

PIP3(C3P,two~F,loc~M)

PIP3 C3P two F loc M

PDK1(PH,STkinase,loc~C)

PDK1 PH STkinase loc C

Akt1(PH,STkinase,T308~O,S473~O,loc~C)

Akt1 PH STkinase T308 O S473 O loc C

KRas(GTPase,g~GDP,loc~M)

KRas GTPase g GDP loc M

p120RasGAP(nSH2,GAP)

p120RasGAP nSH2 GAP

Raf1(RBD,STkinase,S29~O,S43~O,S259~O,S289~O,S296~O,S301~O,S338~O,Y341~O,S471~O,T491~O,S494~O,S642~O,loc~C)

Raf1 RBD STkinase S29 O S43 O S259 O S289 O S296 O S301 O S338 O Y341 O S471 O T491 O S494 O S642 O loc C

MEK1(delta,S218~O,S222~O,T292~O,loc~C)

MEK1 delta S218 O S222 O T292 O loc C

ERK2(CD,STkinase,T185~O,Y187~O,loc~C)

ERK2 CD STkinase T185 O Y187 O loc C

Observables

EGFREGFR EGFR(II!1,loc~M).EGFR(II!1,loc~M)

EGFR ?I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGFR ?I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M

EGFRErbB2 EGFR(II!1,loc~M).ErbB2(II!1,loc~M)

EGFR ?I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M

EGFRErbB3 EGFR(II!1,loc~M).ErbB3(II!1,loc~M)

EGFR ?I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB3 ?I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M

EGFRErbB4 EGFR(II!1,loc~M).ErbB4(II!1,loc~M)

EGFR ?I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB4 ?I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

ErbB2ErbB2 ErbB2(II!1,loc~M).ErbB2(II!1,loc~M)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M

ErbB2ErbB3 ErbB2(II!1,loc~M).ErbB3(II!1,loc~M)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ErbB3 ?I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M

ErbB2ErbB4 ErbB2(II!1,loc~M).ErbB4(II!1,loc~M)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ErbB4 ?I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

ErbB3ErbB3 ErbB3(II!1,loc~M).ErbB3(II!1,loc~M)

ErbB3 ?I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ErbB3 ?I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M

ErbB3ErbB4 ErbB3(II!1,loc~M).ErbB4(II!1,loc~M)

ErbB3 ?I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ErbB4 ?I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

ErbB4ErbB4 ErbB4(II!1,loc~M).ErbB4(II!1,loc~M)

ErbB4 ?I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ErbB4 ?I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

EGFREGFREn EGFR(II!1,loc~En).EGFR(II!1,loc~En)

EGFR ?I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En EGFR ?I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En

EGFRErbB2En EGFR(II!1,loc~En).ErbB2(II!1,loc~En)

EGFR ?I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc En

EGFRErbB3En EGFR(II!1,loc~En).ErbB3(II!1,loc~En)

EGFR ?I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En ErbB3 ?I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En

EGFRErbB4En EGFR(II!1,loc~En).ErbB4(II!1,loc~En)

EGFR ?I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En ErbB4 ?I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En

ErbB2ErbB2En ErbB2(II!1,loc~En).ErbB2(II!1,loc~En)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc En ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc En

ErbB2ErbB3En ErbB2(II!1,loc~En).ErbB3(II!1,loc~En)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc En ErbB3 ?I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En

ErbB2ErbB4En ErbB2(II!1,loc~En).ErbB4(II!1,loc~En)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc En ErbB4 ?I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En

ErbB3ErbB3En ErbB3(II!1,loc~En).ErbB3(II!1,loc~En)

ErbB3 ?I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En ErbB3 ?I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En

ErbB3ErbB4En ErbB3(II!1,loc~En).ErbB4(II!1,loc~En)

ErbB3 ?I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En ErbB4 ?I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En

ErbB4ErbB4En ErbB4(II!1,loc~En).ErbB4(II!1,loc~En)

ErbB4 ?I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En ErbB4 ?I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En

ERK_T185 ERK2(T185~P!?)

ERK2 ?CD ?STkinase T185 ?P Y187 O ?P loc ?C

AKT_S473 Akt1(S473~P!?)

Akt1 ?PH ?STkinase T308 O ?P S473 ?P loc ?C

EGFR_669 EGFR(T669~P!?)

EGFR ?I_III ?II T669 ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

EGFR_992 EGFR(Y992~P!?)

EGFR ?I_III ?II T669 O ?P Y992 ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

EGFR_1068 EGFR(Y1068~P!?)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

EGFR_1086 EGFR(Y1086~P!?)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

EGFR_1114 EGFR(Y1114~P!?)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 ?P Y1148 O ?P Y1173 O ?P loc M ?En

EGFR_1148 EGFR(Y1148~P!?)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 ?P Y1173 O ?P loc M ?En

EGFR_1173 EGFR(Y1173~P!?)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 ?P loc M ?En

ErbB2_1139 ErbB2(Y1139~P!?)

ErbB2 ?II Y1139 ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

ErbB2_1196 ErbB2(Y1196~P!?)

ErbB2 ?II Y1139 O ?P Y1196 ?P Y1222 O ?P Y1248 O ?P loc M ?En

ErbB2_1222 ErbB2(Y1222~P!?)

ErbB2 ?II Y1139 O ?P Y1196 O ?P Y1222 ?P Y1248 O ?P loc M ?En

ErbB2_1248 ErbB2(Y1248~P!?)

ErbB2 ?II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 ?P loc M ?En

ErbB3_1054 ErbB3(Y1054~P!?)

ErbB3 ?I_III ?II Y1054 ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

ErbB3_1197 ErbB3(Y1197~P!?)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

ErbB3_1222 ErbB3(Y1222~P!?)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

ErbB3_1260 ErbB3(Y1260~P!?)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

ErbB3_1276 ErbB3(Y1276~P!?)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 ?P Y1289 O ?P Y1328 O ?P loc M ?En

ErbB3_1289 ErbB3(Y1289~P!?)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 ?P Y1328 O ?P loc M ?En

ErbB3_1328 ErbB3(Y1328~P!?)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 ?P loc M ?En

ErbB4_1056 ErbB4(Y1056~P!?)

ErbB4 ?I_III ?II Y1056 ?P Y1188 O ?P Y1242 O ?P loc M ?En

ErbB4_1188 ErbB4(Y1188~P!?)

ErbB4 ?I_III ?II Y1056 O ?P Y1188 ?P Y1242 O ?P loc M ?En

ErbB4_1242 ErbB4(Y1242~P!?)

ErbB4 ?I_III ?II Y1056 O ?P Y1188 O ?P Y1242 ?P loc M ?En

pSHC p52Shc1(Y317~P!?)

p52Shc1 ?PTB Y317 ?P loc ?C

Sos1_1132 Sos1(S1132~P!?)

Sos1 ?PRS ?REM ?GEF S1132 ?P S1167 O ?P S1178 O ?P S1193 O ?P loc ?C

Sos1_1167 Sos1(S1167~P!?)

Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 ?P S1178 O ?P S1193 O ?P loc ?C

Sos1_1178 Sos1(S1178~P!?)

Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 ?P S1193 O ?P loc ?C

Sos1_1193 Sos1(S1193~P!?)

Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 O ?P S1193 ?P loc ?C

Gab1_312 Gab1(T312~P!?)

Gab1 ?PH ?PRS1_PRS2 T312 ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1_381 Gab1(S381~P!?)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1_447 Gab1(Y447~P!?)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1_454 Gab1(S454~P!?)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1_472 Gab1(Y472~P!?)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1_476 Gab1(T476~P!?)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1_581 Gab1(S581~P!?)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1_597 Gab1(S597~P!?)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 ?P Y619 O ?P Y657 O ?P loc ?C

Gab1_619 Gab1(Y619~P!?)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 ?P Y657 O ?P loc ?C

Gab1_657 Gab1(Y657~P!?)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 ?P loc ?C

Raf1_29 Raf1(S29~P!?)

Raf1 ?RBD ?STkinase S29 ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1_43 Raf1(S43~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1_259 Raf1(S259~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1_289 Raf1(S289~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1_296 Raf1(S296~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1_301 Raf1(S301~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1_338 Raf1(S338~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1_341 Raf1(Y341~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1_471 Raf1(S471~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1_491 Raf1(T491~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 ?P S494 O ?P S642 O ?P loc ?C

Raf1_494 Raf1(S494~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 ?P S642 O ?P loc ?C

Raf1_642 Raf1(S642~P!?)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 ?P loc ?C

MEK1_218 MEK1(S218~P!?)

MEK1 ?delta S218 ?P S222 O ?P T292 O ?P loc ?C

MEK1_222 MEK1(S222~P!?)

MEK1 ?delta S218 O ?P S222 ?P T292 O ?P loc ?C

MEK1_292 MEK1(T292~P!?)

MEK1 ?delta S218 O ?P S222 O ?P T292 ?P loc ?C

pERK_Y187 ERK2(Y187~P!?)

ERK2 ?CD ?STkinase T185 O ?P Y187 ?P loc ?C

AKT_T308 Akt1(T308~P!?)

Akt1 ?PH ?STkinase T308 ?P S473 O ?P loc ?C

Reaction Rules


############# LIGAND BINDING ##############
EGF binding to an EGFR monomer

EGFR(I_III,II,loc~M) + EGF(EGFL,deg~F,loc~Ex) <-> EGFR(I_III!1,II,loc~M).EGF(EGFL!1,deg~F,loc~Ex)

EGFR ⬇⬆I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ⬇⬆ EGF ⬇⬆EGFL deg F loc Ex

HRG binding to an ErbB3 monomer

ErbB3(I_III,II,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> ErbB3(I_III!1,II,loc~M).HRG(EGFL!1,deg~F,loc~Ex)

ErbB3 ⬇⬆I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

HRG binding to an ErbB4 monomer

ErbB4(I_III,II,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> ErbB4(I_III!1,II,loc~M).HRG(EGFL!1,deg~F,loc~Ex)

ErbB4 ⬇⬆I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

EGF binding to an EGFR homodimer

EGFR(I_III,II!1,loc~M).EGFR(I_III,II!1,loc~M) + EGF(EGFL,deg~F,loc~Ex) <-> EGFR(I_III,II!1,loc~M).EGFR(I_III!2,II!1,loc~M).EGF(EGFL!2,deg~F,loc~Ex)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGFR ⬇⬆I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ⬇⬆ EGF ⬇⬆EGFL deg F loc Ex

EGF(EGFL!2,deg~F,loc~Ex).EGFR(I_III!2,II!1,loc~M).EGFR(I_III,II!1,loc~M) + EGF(EGFL,deg~F,loc~Ex) <-> EGF(EGFL!2,deg~F,loc~Ex).EGFR(I_III!2,II!1,loc~M).EGFR(I_III!3,II!1,loc~M).EGF(EGFL!3,deg~F,loc~Ex)

EGF EGFL deg F loc Ex EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGFR ⬇⬆I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ⬇⬆ EGF ⬇⬆EGFL deg F loc Ex

EGF binding to an EGFR-ErbB2 heterodimer

ErbB2(II!1,loc~M).EGFR(I_III,II!1,loc~M) + EGF(EGFL,deg~F,loc~Ex) <-> ErbB2(II!1,loc~M).EGFR(I_III!2,II!1,loc~M).EGF(EGFL!2,deg~F,loc~Ex)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M EGFR ⬇⬆I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ⬇⬆ EGF ⬇⬆EGFL deg F loc Ex

Ligand binding to an EGFR-ErbB3 heterodimer

EGF(EGFL,deg~F,loc~Ex) + EGFR(I_III,II!1,loc~M).ErbB3(I_III,II!1,loc~M) <-> EGF(EGFL!2,deg~F,loc~Ex).EGFR(I_III!2,II!1,loc~M).ErbB3(I_III,II!1,loc~M)

EGF ⬇⬆EGFL deg F loc Ex ⬇⬆ EGFR ⬇⬆I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M

EGFR(I_III,II!1,loc~M).ErbB3(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> EGFR(I_III,II!1,loc~M).ErbB3(I_III!2,II!1,loc~M).HRG(EGFL!2,deg~F,loc~Ex)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB3 ⬇⬆I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

EGF(EGFL!2,deg~F,loc~Ex).EGFR(I_III!2,II!1,loc~M).ErbB3(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> EGF(EGFL!2,deg~F,loc~Ex).EGFR(I_III!2,II!1,loc~M).ErbB3(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex)

EGF EGFL deg F loc Ex EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB3 ⬇⬆I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

EGF(EGFL,deg~F,loc~Ex) + EGFR(I_III,II!1,loc~M).ErbB3(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex) <-> EGF(EGFL!2,deg~F,loc~Ex).EGFR(I_III!2,II!1,loc~M).ErbB3(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex)

EGF ⬇⬆EGFL deg F loc Ex ⬇⬆ EGFR ⬇⬆I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M HRG EGFL deg F loc Ex

Ligand binding to an EGFR-ErbB4 heterodimer

EGF(EGFL,deg~F,loc~Ex) + EGFR(I_III,II!1,loc~M).ErbB4(I_III,II!1,loc~M) <-> EGF(EGFL!2,deg~F,loc~Ex).EGFR(I_III!2,II!1,loc~M).ErbB4(I_III,II!1,loc~M)

EGF ⬇⬆EGFL deg F loc Ex ⬇⬆ EGFR ⬇⬆I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

EGFR(I_III,II!1,loc~M).ErbB4(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> EGFR(I_III,II!1,loc~M).ErbB4(I_III!2,II!1,loc~M).HRG(EGFL!2,deg~F,loc~Ex)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB4 ⬇⬆I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

EGF(EGFL!2,deg~F,loc~Ex).EGFR(I_III!2,II!1,loc~M).ErbB4(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> EGF(EGFL!2,deg~F,loc~Ex).EGFR(I_III!2,II!1,loc~M).ErbB4(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex)

EGF EGFL deg F loc Ex EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB4 ⬇⬆I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

EGF(EGFL,deg~F,loc~Ex) + EGFR(I_III,II!1,loc~M).ErbB4(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex) <-> EGF(EGFL!2,deg~F,loc~Ex).EGFR(I_III!2,II!1,loc~M).ErbB4(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex)

EGF ⬇⬆EGFL deg F loc Ex ⬇⬆ EGFR ⬇⬆I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M HRG EGFL deg F loc Ex

HRG binding to an ErbB2-ErbB3 heterodimer

ErbB2(II!1,loc~M).ErbB3(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> ErbB2(II!1,loc~M).ErbB3(I_III!2,II!1,loc~M).HRG(EGFL!2,deg~F,loc~Ex)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ErbB3 ⬇⬆I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

HRG binding to an ErbB2-ErbB4 heterodimer

ErbB2(II!1,loc~M).ErbB4(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> ErbB2(II!1,loc~M).ErbB4(I_III!2,II!1,loc~M).HRG(EGFL!2,deg~F,loc~Ex)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ErbB4 ⬇⬆I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

HRG binding to an ErbB3 homodimer

ErbB3(I_III,II!1,loc~M).ErbB3(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> ErbB3(I_III,II!1,loc~M).ErbB3(I_III!2,II!1,loc~M).HRG(EGFL!2,deg~F,loc~Ex)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ErbB3 ⬇⬆I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

HRG(EGFL!2,deg~F,loc~Ex).ErbB3(I_III!2,II!1,loc~M).ErbB3(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> HRG(EGFL!2,deg~F,loc~Ex).ErbB3(I_III!2,II!1,loc~M).ErbB3(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex)

HRG EGFL deg F loc Ex ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ErbB3 ⬇⬆I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

Ligand binding to an ErbB3-ErbB4 heterodimer

ErbB3(I_III,II!1,loc~M).ErbB4(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> ErbB3(I_III,II!1,loc~M).ErbB4(I_III!2,II!1,loc~M).HRG(EGFL!2,deg~F,loc~Ex)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ErbB4 ⬇⬆I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

HRG(EGFL,deg~F,loc~Ex) + ErbB3(I_III,II!1,loc~M).ErbB4(I_III,II!1,loc~M) <-> HRG(EGFL!2,deg~F,loc~Ex).ErbB3(I_III!2,II!1,loc~M).ErbB4(I_III,II!1,loc~M)

HRG ⬇⬆EGFL deg F loc Ex ⬇⬆ ErbB3 ⬇⬆I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

HRG(EGFL!2,deg~F,loc~Ex).ErbB3(I_III!2,II!1,loc~M).ErbB4(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> HRG(EGFL!2,deg~F,loc~Ex).ErbB3(I_III!2,II!1,loc~M).ErbB4(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex)

HRG EGFL deg F loc Ex ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ErbB4 ⬇⬆I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

HRG(EGFL,deg~F,loc~Ex) + ErbB3(I_III,II!1,loc~M).ErbB4(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex) <-> HRG(EGFL!2,deg~F,loc~Ex).ErbB3(I_III!2,II!1,loc~M).ErbB4(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex)

HRG ⬇⬆EGFL deg F loc Ex ⬇⬆ ErbB3 ⬇⬆I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M HRG EGFL deg F loc Ex

HRG binding to an ErbB4 homodimer

ErbB4(I_III,II!1,loc~M).ErbB4(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> ErbB4(I_III,II!1,loc~M).ErbB4(I_III!2,II!1,loc~M).HRG(EGFL!2,deg~F,loc~Ex)

ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ErbB4 ⬇⬆I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

HRG(EGFL!2,deg~F,loc~Ex).ErbB4(I_III!2,II!1,loc~M).ErbB4(I_III,II!1,loc~M) + HRG(EGFL,deg~F,loc~Ex) <-> HRG(EGFL!2,deg~F,loc~Ex).ErbB4(I_III!2,II!1,loc~M).ErbB4(I_III!3,II!1,loc~M).HRG(EGFL!3,deg~F,loc~Ex)

HRG EGFL deg F loc Ex ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ErbB4 ⬇⬆I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ⬇⬆ HRG ⬇⬆EGFL deg F loc Ex

############# RECEPTOR DIMERIZATION ##############
EGFR-EGFR
EGFR-EGFR dimerization with no EGF bound

EGFR(I_III,II,loc~M) + EGFR(I_III,II,loc~M) <-> EGFR(I_III,II!1,loc~M).EGFR(I_III,II!1,loc~M)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ⬇⬆ EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M

EGFR-EGFR dimerization with one EGF bound

EGFR(I_III!1,II,loc~M).EGF(EGFL!1,loc~Ex) + EGFR(I_III,II,loc~M) <-> EGFR(I_III!1,II!2,loc~M).EGF(EGFL!1,loc~Ex).EGFR(I_III,II!2,loc~M)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGF EGFL deg F ?T loc Ex ⬇⬆ EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M

EGFR-EGFR dimerization with two EGF bound

EGFR(I_III!1,II,loc~M).EGF(EGFL!1,loc~Ex) + EGFR(I_III!2,II,loc~M).EGF(EGFL!2,loc~Ex) <-> EGFR(I_III!1,II!3,loc~M).EGF(EGFL!1,loc~Ex).EGFR(I_III!2,II!3,loc~M).EGF(EGFL!2,loc~Ex)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGF EGFL deg F ?T loc Ex ⬇⬆ EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGF EGFL deg F ?T loc Ex

EGFR-ErbB2
EGFR-ErbB2 dimerization with no EGF bound

EGFR(I_III,II,loc~M) + ErbB2(II,loc~M) <-> EGFR(I_III,II!1,loc~M).ErbB2(II!1,loc~M)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ⬇⬆ ErbB2 ⬇⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M

EGFR-ErbB2 dimerization with EGF bound

EGFR(I_III!1,II,loc~M).EGF(EGFL!1,loc~Ex) + ErbB2(II,loc~M) <-> EGFR(I_III!1,II!2,loc~M).EGF(EGFL!1,loc~Ex).ErbB2(II!2,loc~M)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGF EGFL deg F ?T loc Ex ⬇⬆ ErbB2 ⬇⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M

EGFR-ErbB3
EGFR-ErbB3 dimerization with no ligand bound

EGFR(I_III,II,loc~M) + ErbB3(I_III,II,loc~M) <-> EGFR(I_III,II!1,loc~M).ErbB3(I_III,II!1,loc~M)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ⬇⬆ ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M

EGFR-ErbB3 dimerization with EGF bound

EGFR(I_III!1,II,loc~M).EGF(EGFL!1,loc~Ex) + ErbB3(I_III,II,loc~M) <-> EGFR(I_III!1,II!2,loc~M).EGF(EGFL!1,loc~Ex).ErbB3(I_III,II!2,loc~M)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGF EGFL deg F ?T loc Ex ⬇⬆ ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M

EGFR-ErbB3 dimerization with HRG bound

ErbB3(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) + EGFR(I_III,II,loc~M) <-> ErbB3(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).EGFR(I_III,II!2,loc~M)

ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M HRG EGFL deg F ?T loc Ex ⬇⬆ EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M

EGFR-ErbB3 dimerization with EGF and HRG bound

EGFR(I_III!1,II,loc~M).EGF(EGFL!1,loc~Ex) + ErbB3(I_III!2,II,loc~M).HRG(EGFL!2,loc~Ex) <-> EGFR(I_III!1,II!3,loc~M).EGF(EGFL!1,loc~Ex).ErbB3(I_III!2,II!3,loc~M).HRG(EGFL!2,loc~Ex)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGF EGFL deg F ?T loc Ex ⬇⬆ ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M HRG EGFL deg F ?T loc Ex

EGFR-ErbB4
EGFR-ErbB4 dimerization with no ligand bound

EGFR(I_III,II,loc~M) + ErbB4(I_III,II,loc~M) <-> EGFR(I_III,II!1,loc~M).ErbB4(I_III,II!1,loc~M)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

EGFR-ErbB4 dimerization with EGF bound

EGFR(I_III!1,II,loc~M).EGF(EGFL!1,loc~Ex) + ErbB4(I_III,II,loc~M) <-> EGFR(I_III!1,II!2,loc~M).EGF(EGFL!1,loc~Ex).ErbB4(I_III,II!2,loc~M)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGF EGFL deg F ?T loc Ex ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

EGFR-ErbB4 dimerization with HRG bound

ErbB4(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) + EGFR(I_III,II,loc~M) <-> ErbB4(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).EGFR(I_III,II!2,loc~M)

ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M HRG EGFL deg F ?T loc Ex ⬇⬆ EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M

EGFR-ErbB4 dimerization with EGF and HRG bound

EGFR(I_III!1,II,loc~M).EGF(EGFL!1,loc~Ex) + ErbB4(I_III!2,II,loc~M).HRG(EGFL!2,loc~Ex) <-> EGFR(I_III!1,II!3,loc~M).EGF(EGFL!1,loc~Ex).ErbB4(I_III!2,II!3,loc~M).HRG(EGFL!2,loc~Ex)

EGFR I_III ⬇⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M EGF EGFL deg F ?T loc Ex ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M HRG EGFL deg F ?T loc Ex

ErbB2-ErbB2 dimerization

ErbB2(II,loc~M) + ErbB2(II,loc~M) <-> ErbB2(II!1,loc~M).ErbB2(II!1,loc~M)

ErbB2 ⬇⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ⬇⬆ ErbB2 ⬇⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M

ErbB2-ErbB3
ErbB2-ErbB3 dimerization with no ligand bound

ErbB2(II,loc~M) + ErbB3(I_III,II,loc~M) <-> ErbB2(II!1,loc~M).ErbB3(I_III,II!1,loc~M)

ErbB2 ⬇⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ⬇⬆ ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M

ErbB2-ErbB3 dimerization with HRG bound

ErbB3(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) + ErbB2(II,loc~M) <-> ErbB3(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB2(II!2,loc~M)

ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M HRG EGFL deg F ?T loc Ex ⬇⬆ ErbB2 ⬇⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M

ErbB2-ErbB4
ErbB2-ErbB4 dimerization with no ligand bound

ErbB2(II,loc~M) + ErbB4(I_III,II,loc~M) <-> ErbB2(II!1,loc~M).ErbB4(I_III,II!1,loc~M)

ErbB2 ⬇⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

ErbB2-ErbB4 dimerization with HRG bound

ErbB4(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) + ErbB2(II,loc~M) <-> ErbB4(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB2(II!2,loc~M)

ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M HRG EGFL deg F ?T loc Ex ⬇⬆ ErbB2 ⬇⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M

ErbB3-ErbB3
ErbB3-ErbB3 dimerization with no HRG bound

ErbB3(I_III,II,loc~M) + ErbB3(I_III,II,loc~M) <-> ErbB3(I_III,II!1,loc~M).ErbB3(I_III,II!1,loc~M)

ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ⬇⬆ ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M

ErbB3-ErbB3 dimerization with one HRG bound

ErbB3(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) + ErbB3(I_III,II,loc~M) <-> ErbB3(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB3(I_III,II!2,loc~M)

ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M HRG EGFL deg F ?T loc Ex ⬇⬆ ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M

ErbB3-ErbB3 dimerization with two HRG bound

ErbB3(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) + ErbB3(I_III!2,II,loc~M).HRG(EGFL!2,loc~Ex) <-> ErbB3(I_III!1,II!3,loc~M).HRG(EGFL!1,loc~Ex).ErbB3(I_III!2,II!3,loc~M).HRG(EGFL!2,loc~Ex)

ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M HRG EGFL deg F ?T loc Ex ⬇⬆ ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M HRG EGFL deg F ?T loc Ex

ErbB3-ErbB4
ErbB3-ErbB4 dimerization with no HRG bound

ErbB3(I_III,II,loc~M) + ErbB4(I_III,II,loc~M) <-> ErbB3(I_III,II!1,loc~M).ErbB4(I_III,II!1,loc~M)

ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

ErbB3-ErbB4 dimerization with HRG bound on ErbB3

ErbB3(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) + ErbB4(I_III,II,loc~M) <-> ErbB3(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB4(I_III,II!2,loc~M)

ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M HRG EGFL deg F ?T loc Ex ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

ErbB3-ErbB4 dimerization with HRG bound on ErbB4

ErbB3(I_III,II,loc~M) + ErbB4(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) <-> ErbB3(I_III,II!2,loc~M).ErbB4(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex)

ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M HRG EGFL deg F ?T loc Ex

ErbB3-ErbB4 dimerization with HRG bound on both receptors

ErbB3(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) + ErbB4(I_III!2,II,loc~M).HRG(EGFL!2,loc~Ex) <-> ErbB3(I_III!1,II!3,loc~M).HRG(EGFL!1,loc~Ex).ErbB4(I_III!2,II!3,loc~M).HRG(EGFL!2,loc~Ex)

ErbB3 I_III ⬇⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M HRG EGFL deg F ?T loc Ex ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M HRG EGFL deg F ?T loc Ex

ErbB4-ErbB4
ErbB4-ErbB4 dimerization with no HRG bound

ErbB4(I_III,II,loc~M) + ErbB4(I_III,II,loc~M) <-> ErbB4(I_III,II!1,loc~M).ErbB4(I_III,II!1,loc~M)

ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

ErbB4-ErbB4 dimerization with one HRG bound

ErbB4(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) + ErbB4(I_III,II,loc~M) <-> ErbB4(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB4(I_III,II!2,loc~M)

ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M HRG EGFL deg F ?T loc Ex ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M

ErbB4-ErbB4 dimerization with two HRG bound

ErbB4(I_III!1,II,loc~M).HRG(EGFL!1,loc~Ex) + ErbB4(I_III!2,II,loc~M).HRG(EGFL!2,loc~Ex) <-> ErbB4(I_III!1,II!3,loc~M).HRG(EGFL!1,loc~Ex).ErbB4(I_III!2,II!3,loc~M).HRG(EGFL!2,loc~Ex)

ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M HRG EGFL deg F ?T loc Ex ⬇⬆ ErbB4 I_III ⬇⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M HRG EGFL deg F ?T loc Ex

############# RECEPTOR INTERNALIZATION ##############
EGFR-EGFR
EGFR-EGFR dimers get internalized with two EGF bound

EGFR(I_III!1,II!3,loc~M).EGF(EGFL!1,loc~Ex).EGFR(I_III!2,II!3,loc~M).EGF(EGFL!2,loc~Ex) -> EGFR(I_III!1,II!3,loc~En).EGF(EGFL!1,loc~En).EGFR(I_III!2,II!3,loc~En).EGF(EGFL!2,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ EGF EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ EGF EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇

EGFR-EGFR dimers get internalized with one EGF bound

EGFR(I_III!1,II!2,loc~M).EGF(EGFL!1,loc~Ex).EGFR(I_III,II!2,loc~M) -> EGFR(I_III!1,II!2,loc~En).EGF(EGFL!1,loc~En).EGFR(I_III,II!2,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ EGF EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇

EGFR-EGFR dimers get internalized with no ligand bound

EGFR(I_III,II!2,loc~M).EGFR(I_III,II!2,loc~M) -> EGFR(I_III,II!2,loc~En).EGFR(I_III,II!2,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇

EGFR-ErbB2 dimers get internalized with EGF bound

EGFR(I_III!1,II!2,loc~M).EGF(EGFL!1,loc~Ex).ErbB2(II!2,loc~M) -> EGFR(I_III!1,II!2,loc~En).EGF(EGFL!1,loc~En).ErbB2(II!2,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ EGF EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M En take all branches, once each, in any order⬇

EGFR-ErbB2 dimers get internalized with no ligand bound

EGFR(I_III,II!2,loc~M).ErbB2(II!2,loc~M) -> EGFR(I_III,II!2,loc~En).ErbB2(II!2,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M En take all branches, once each, in any order⬇

EGFR-ErbB3 dimers get internalized with EGF and HRG bound

EGFR(I_III!1,II!3,loc~M).EGF(EGFL!1,loc~Ex).ErbB3(I_III!2,II!3,loc~M).HRG(EGFL!2,loc~Ex) -> EGFR(I_III!1,II!3,loc~En).EGF(EGFL!1,loc~En).ErbB3(I_III!2,II!3,loc~En).HRG(EGFL!2,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ EGF EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇

EGFR-ErbB3 dimers get internalized with HRG bound

EGFR(I_III,II!3,loc~M).ErbB3(I_III!2,II!3,loc~M).HRG(EGFL!2,loc~Ex) -> EGFR(I_III,II!3,loc~En).ErbB3(I_III!2,II!3,loc~En).HRG(EGFL!2,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇

EGFR-ErbB3 dimers get internalized with EGF bound

EGFR(I_III!1,II!3,loc~M).EGF(EGFL!1,loc~Ex).ErbB3(I_III,II!3,loc~M) -> EGFR(I_III!1,II!3,loc~En).EGF(EGFL!1,loc~En).ErbB3(I_III,II!3,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ EGF EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇

EGFR-ErbB3 dimers get internalized with no ligand bound

EGFR(I_III,II!3,loc~M).ErbB3(I_III,II!3,loc~M) -> EGFR(I_III,II!3,loc~En).ErbB3(I_III,II!3,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇

EGFR-ErbB4 dimers get internalized with EGF and HRG bound

EGFR(I_III!1,II!3,loc~M).EGF(EGFL!1,loc~Ex).ErbB4(I_III!2,II!3,loc~M).HRG(EGFL!2,loc~Ex) -> EGFR(I_III!1,II!3,loc~En).EGF(EGFL!1,loc~En).ErbB4(I_III!2,II!3,loc~En).HRG(EGFL!2,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ EGF EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇

EGFR-ErbB4 dimers get internalized with HRG bound

EGFR(I_III,II!3,loc~M).ErbB4(I_III!2,II!3,loc~M).HRG(EGFL!2,loc~Ex) -> EGFR(I_III,II!3,loc~En).ErbB4(I_III!2,II!3,loc~En).HRG(EGFL!2,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇

EGFR-ErbB4 dimers get internalized with EGF bound

EGFR(I_III!1,II!3,loc~M).EGF(EGFL!1,loc~Ex).ErbB4(I_III,II!3,loc~M) -> EGFR(I_III!1,II!3,loc~En).EGF(EGFL!1,loc~En).ErbB4(I_III,II!3,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ EGF EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇

EGFR-ErbB4 dimers get internalized with no ligand bound

EGFR(I_III,II!3,loc~M).ErbB4(I_III,II!3,loc~M) -> EGFR(I_III,II!3,loc~En).ErbB4(I_III,II!3,loc~En)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇

ErbB2-ErbB2 dimers get internalized

ErbB2(II!1,loc~M).ErbB2(II!1,loc~M) -> ErbB2(II!1,loc~En).ErbB2(II!1,loc~En)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M En take all branches, once each, in any order⬇ ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M En take all branches, once each, in any order⬇

ErbB3-ErbB2 dimers get internalized with HRG bound

ErbB3(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB2(II!2,loc~M) -> ErbB3(I_III!1,II!2,loc~En).HRG(EGFL!1,loc~En).ErbB2(II!2,loc~En)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M En take all branches, once each, in any order⬇

ErbB3-ErbB2 dimers get internalized with no ligand bound

ErbB3(I_III,II!2,loc~M).ErbB2(II!2,loc~M) -> ErbB3(I_III,II!2,loc~En).ErbB2(II!2,loc~En)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M En take all branches, once each, in any order⬇

ErbB4-ErbB2 dimers get internalized with HRG bound

ErbB4(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB2(II!2,loc~M) -> ErbB4(I_III!1,II!2,loc~En).HRG(EGFL!1,loc~En).ErbB2(II!2,loc~En)

ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M En take all branches, once each, in any order⬇

ErbB4-ErbB2 dimers get internalized with no ligand bound

ErbB4(I_III,II!2,loc~M).ErbB2(II!2,loc~M) -> ErbB4(I_III,II!2,loc~En).ErbB2(II!2,loc~En)

ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇ ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M En take all branches, once each, in any order⬇

ErbB3-ErbB3 dimers get internalized with two HRG bound

ErbB3(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB3(I_III!3,II!2,loc~M).HRG(EGFL!3,loc~Ex) -> ErbB3(I_III!1,II!2,loc~En).HRG(EGFL!1,loc~En).ErbB3(I_III!3,II!2,loc~En).HRG(EGFL!3,loc~En)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇

ErbB3-ErbB3 dimers get internalized with one HRG bound

ErbB3(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB3(I_III,II!2,loc~M) -> ErbB3(I_III!1,II!2,loc~En).HRG(EGFL!1,loc~En).ErbB3(I_III,II!2,loc~En)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇

ErbB3-ErbB3 dimers get internalized with no HRG bound

ErbB3(I_III,II!2,loc~M).ErbB3(I_III,II!2,loc~M) -> ErbB3(I_III,II!2,loc~En).ErbB3(I_III,II!2,loc~En)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇

ErbB3-ErbB4 dimers get internalized with two HRG bound

ErbB3(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB4(I_III!3,II!2,loc~M).HRG(EGFL!3,loc~Ex) -> ErbB3(I_III!1,II!2,loc~En).HRG(EGFL!1,loc~En).ErbB4(I_III!3,II!2,loc~En).HRG(EGFL!3,loc~En)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇

ErbB3-ErbB4 dimers get internalized with HRG bound to ErbB3

ErbB3(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB4(I_III,II!2,loc~M) -> ErbB3(I_III!1,II!2,loc~En).HRG(EGFL!1,loc~En).ErbB4(I_III,II!2,loc~En)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇

ErbB3-ErbB4 dimers get internalized with HRG bound to ErbB4

ErbB3(I_III,II!2,loc~M).ErbB4(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex) -> ErbB3(I_III,II!2,loc~En).ErbB4(I_III!1,II!2,loc~En).HRG(EGFL!1,loc~En)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇

ErbB3-ErbB4 dimers get internalized with no HRG bound to both receptors

ErbB3(I_III,II!2,loc~M).ErbB4(I_III,II!2,loc~M) -> ErbB3(I_III,II!2,loc~En).ErbB4(I_III,II!2,loc~En)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇

ErbB4-ErbB4 dimers get internalized with two HRG bound

ErbB4(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB4(I_III!3,II!2,loc~M).HRG(EGFL!3,loc~Ex) -> ErbB4(I_III!1,II!2,loc~En).HRG(EGFL!1,loc~En).ErbB4(I_III!3,II!2,loc~En).HRG(EGFL!3,loc~En)

ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇

ErbB4-ErbB4 dimers get internalized with one HRG bound

ErbB4(I_III!1,II!2,loc~M).HRG(EGFL!1,loc~Ex).ErbB4(I_III,II!2,loc~M) -> ErbB4(I_III!1,II!2,loc~En).HRG(EGFL!1,loc~En).ErbB4(I_III,II!2,loc~En)

ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇ HRG EGFL deg F ?T loc Ex En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇

ErbB4-ErbB4 dimers get internalized with no HRG bound

ErbB4(I_III,II!2,loc~M).ErbB4(I_III,II!2,loc~M) -> ErbB4(I_III,II!2,loc~En).ErbB4(I_III,II!2,loc~En)

ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇ ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take all branches, once each, in any order⬇

internalized EGFR releases ligand

EGFR(I_III!1,loc~En).EGF(EGFL!1,deg~F,loc~En) -> EGFR(I_III,loc~En) + EGF(EGFL,deg~F,loc~En)

EGFR ⬆I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En ⬆ EGF ⬆EGFL deg F loc En

internalized ErbB3 releases ligand

ErbB3(I_III!1,loc~En).HRG(EGFL!1,deg~F,loc~En) -> ErbB3(I_III,loc~En) + HRG(EGFL,deg~F,loc~En)

ErbB3 ⬆I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En ⬆ HRG ⬆EGFL deg F loc En

internalized ErbB4 releases ligand

ErbB4(I_III!1,loc~En).HRG(EGFL!1,deg~F,loc~En) -> ErbB4(I_III,loc~En) + HRG(EGFL,deg~F,loc~En)

ErbB4 ⬆I_III ?II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En ⬆ HRG ⬆EGFL deg F loc En

internalized ligand gets degraded

EGF(EGFL,deg~F,loc~En) -> EGF(EGFL,deg~T,loc~En)

EGF EGFL deg F T take all branches, once each, in any order⬇ loc En

HRG(EGFL,deg~F,loc~En) -> HRG(EGFL,deg~T,loc~En)

HRG EGFL deg F T take all branches, once each, in any order⬇ loc En

internalized receptors dissociate

EGFR(II!3,loc~En).EGFR(II!3,loc~En) -> EGFR(II,loc~En) + EGFR(II,loc~En)

EGFR ?I_III ⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En ⬆ EGFR ?I_III ⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En

EGFR(II!2,loc~En).ErbB2(II!2,loc~En) -> EGFR(II,loc~En) + ErbB2(II,loc~En)

EGFR ?I_III ⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En ⬆ ErbB2 ⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc En

EGFR(II!3,loc~En).ErbB3(II!3,loc~En) -> EGFR(II,loc~En) + ErbB3(II,loc~En)

EGFR ?I_III ⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En ⬆ ErbB3 ?I_III ⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En

EGFR(II!3,loc~En).ErbB4(II!3,loc~En) -> EGFR(II,loc~En) + ErbB4(II,loc~En)

EGFR ?I_III ⬆II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc En ⬆ ErbB4 ?I_III ⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En

ErbB2(II!2,loc~En).ErbB2(II!2,loc~En) -> ErbB2(II,loc~En) + ErbB2(II,loc~En)

ErbB2 ⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc En ⬆ ErbB2 ⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc En

ErbB2(II!2,loc~En).ErbB3(II!2,loc~En) -> ErbB2(II,loc~En) + ErbB3(II,loc~En)

ErbB2 ⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc En ⬆ ErbB3 ?I_III ⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En

ErbB2(II!2,loc~En).ErbB4(II!2,loc~En) -> ErbB2(II,loc~En) + ErbB4(II,loc~En)

ErbB2 ⬆II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc En ⬆ ErbB4 ?I_III ⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En

ErbB3(II!2,loc~En).ErbB3(II!2,loc~En) -> ErbB3(II,loc~En) + ErbB3(II,loc~En)

ErbB3 ?I_III ⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En ⬆ ErbB3 ?I_III ⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En

ErbB3(II!2,loc~En).ErbB4(II!2,loc~En) -> ErbB3(II,loc~En) + ErbB4(II,loc~En)

ErbB3 ?I_III ⬆II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc En ⬆ ErbB4 ?I_III ⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En

ErbB4(II!2,loc~En).ErbB4(II!2,loc~En) -> ErbB4(II,loc~En) + ErbB4(II,loc~En)

ErbB4 ?I_III ⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En ⬆ ErbB4 ?I_III ⬆II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc En

non-dimerized receptors with no ligand bound return to the membrane

EGFR(I_III,II,loc~En) -> EGFR(I_III,II,loc~M)

EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M En take one or more branches, once each, in any order⬆

ErbB2(II,loc~En) -> ErbB2(II,loc~M)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M En take one or more branches, once each, in any order⬆

ErbB3(I_III,II,loc~En) -> ErbB3(I_III,II,loc~M)

ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M En take one or more branches, once each, in any order⬆

ErbB4(I_III,II,loc~En) -> ErbB4(I_III,II,loc~M)

ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M En take one or more branches, once each, in any order⬆

############# RECEPTOR CROSS-PHOSPHORYLATION ##############
Receptor Phosphorylation Reactions
NOTE: The philosophy of these rules is that both ligand binding sites in a dimer must be occupied in order for kinase domains to be active
# EGFR
# (EGFR-EGFR dimers)(992,1068,1086,1114,1148,1173)
# (ErbB2-EGFR dimers)(992,1068,1086,1114,1148,1173)
# (ErbB4-EGFR dimers)(992,1068,1086,1114,1148,1173)
# ErbB2
# (EGFR-ErbB2 dimers)(1139,1196,1222,1248)
# (ErbB4-ErbB2 dimers)(1139,1196,1222,1248)
# ErbB3
# (EGFR-ErbB3 dimers)(1054,1197,1222,Y1260,1276,1289,1328)
# (ErbB2-ErbB3 dimers)(1054,1197,1222,Y1260,1276,1289,1328)
# (ErbB4-ErbB3 dimers)(1054,1197,1222,Y1260,1276,1289,1328)
# ErbB4
# (EGFR-ErbB4 dimers)(1056,1188,1242)
# (ErbB2-ErbB4 dimers)(1056,1188,1242)
# (ErbB4-ErbB4 dimers)(1056,1188,1242)
# -----------------------------------------
cross-phosphorylation of EGFR
(EGFR-EGFR dimers) Cross-Phosphorylation of EGFR by EGFR at
(992,1068,1086,1114,1148,1173)

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y992~O).EGF(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y992~P).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O P take all branches, once each, in any order⬇ Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y1068~O).EGF(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y1068~P).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O P take all branches, once each, in any order⬇ Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y1086~O).EGF(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y1086~P).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O P take all branches, once each, in any order⬇ Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y1114~O).EGF(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y1114~P).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O P take all branches, once each, in any order⬇ Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y1148~O).EGF(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y1148~P).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O P take all branches, once each, in any order⬇ Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y1173~O).EGF(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).EGFR(I_III!3,II!1,Y1173~P).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O P take all branches, once each, in any order⬇ loc M ?En EGF EGFL deg F ?T loc Ex ?En

(ErbB2-EGFR dimers) Cross-Phosphorylation of EGFR by ErbB2 at
(992,1068,1086,1114,1148,1173)

ErbB2(II!1).EGFR(I_III!3,II!1,Y992~O).EGF(EGFL!3) -> ErbB2(II!1).EGFR(I_III!3,II!1,Y992~P).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O P take all branches, once each, in any order⬇ Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).EGFR(I_III!3,II!1,Y1068~O).EGF(EGFL!3) -> ErbB2(II!1).EGFR(I_III!3,II!1,Y1068~P).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O P take all branches, once each, in any order⬇ Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).EGFR(I_III!3,II!1,Y1086~O).EGF(EGFL!3) -> ErbB2(II!1).EGFR(I_III!3,II!1,Y1086~P).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O P take all branches, once each, in any order⬇ Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).EGFR(I_III!3,II!1,Y1114~O).EGF(EGFL!3) -> ErbB2(II!1).EGFR(I_III!3,II!1,Y1114~P).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O P take all branches, once each, in any order⬇ Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).EGFR(I_III!3,II!1,Y1148~O).EGF(EGFL!3) -> ErbB2(II!1).EGFR(I_III!3,II!1,Y1148~P).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O P take all branches, once each, in any order⬇ Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).EGFR(I_III!3,II!1,Y1173~O).EGF(EGFL!3) -> ErbB2(II!1).EGFR(I_III!3,II!1,Y1173~P).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O P take all branches, once each, in any order⬇ loc M ?En EGF EGFL deg F ?T loc Ex ?En

(ErbB4-EGFR dimers) Cross-Phosphorylation of EGFR by ErbB4 at
(992,1068,1086,1114,1148,1173)

HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y992~O).EGF(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y992~P).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O P take all branches, once each, in any order⬇ Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y1068~O).EGF(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y1068~P).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O P take all branches, once each, in any order⬇ Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y1086~O).EGF(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y1086~P).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O P take all branches, once each, in any order⬇ Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y1114~O).EGF(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y1114~P).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O P take all branches, once each, in any order⬇ Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y1148~O).EGF(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y1148~P).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O P take all branches, once each, in any order⬇ Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y1173~O).EGF(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).EGFR(I_III!3,II!1,Y1173~P).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O P take all branches, once each, in any order⬇ loc M ?En EGF EGFL deg F ?T loc Ex ?En

Cross-phosphorylation of ErbB2
(EGFR-ErbB2 dimers) Cross-Phosphorylation of ErbB2 by EGFR at
(1139,1196,1222,1248)

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB2(II!1,Y1139~O) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB2(II!1,Y1139~P)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB2 II Y1139 O P take all branches, once each, in any order⬇ Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB2(II!1,Y1196~O) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB2(II!1,Y1196~P)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB2 II Y1139 O ?P Y1196 O P take all branches, once each, in any order⬇ Y1222 O ?P Y1248 O ?P loc M ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB2(II!1,Y1222~O) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB2(II!1,Y1222~P)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O P take all branches, once each, in any order⬇ Y1248 O ?P loc M ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB2(II!1,Y1248~O) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB2(II!1,Y1248~P)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O P take all branches, once each, in any order⬇ loc M ?En

Cross-phosphorylation of ErbB2
(ErbB4-ErbB2 dimers) Cross-Phosphorylation of ErbB2 by ErbB4 at
(1139,1196,1222,1248)

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB2(II!1,Y1139~O) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB2(II!1,Y1139~P)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB2 II Y1139 O P take all branches, once each, in any order⬇ Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB2(II!1,Y1196~O) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB2(II!1,Y1196~P)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB2 II Y1139 O ?P Y1196 O P take all branches, once each, in any order⬇ Y1222 O ?P Y1248 O ?P loc M ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB2(II!1,Y1222~O) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB2(II!1,Y1222~P)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O P take all branches, once each, in any order⬇ Y1248 O ?P loc M ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB2(II!1,Y1248~O) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB2(II!1,Y1248~P)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O P take all branches, once each, in any order⬇ loc M ?En

cross-phosphorylation of ErbB3
(EGFR-ErbB3 dimers) cross-phosphorylation of ErbB3 by EGFR at
(1054,1197,1222,Y1260,1276,1289,1328)

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1054~O).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1054~P).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB3 I_III II Y1054 O P take all branches, once each, in any order⬇ Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1197~O).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1197~P).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O P take all branches, once each, in any order⬇ Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1222~O).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1222~P).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O P take all branches, once each, in any order⬇ Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1260~O).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1260~P).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O P take all branches, once each, in any order⬇ Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1276~O).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1276~P).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O P take all branches, once each, in any order⬇ Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1289~O).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1289~P).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O P take all branches, once each, in any order⬇ Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1328~O).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB3(I_III!3,II!1,Y1328~P).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O P take all branches, once each, in any order⬇ loc M ?En HRG EGFL deg F ?T loc Ex ?En

(ErbB2-ErbB3 dimers) cross-phosphorylation of Erbb3 by ErbB2 at
(1054,1197,1222,Y1260,1276,1289,1328)

ErbB2(II!1).ErbB3(I_III!3,II!1,Y1054~O).HRG(EGFL!3) -> ErbB2(II!1).ErbB3(I_III!3,II!1,Y1054~P).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ErbB3 I_III II Y1054 O P take all branches, once each, in any order⬇ Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).ErbB3(I_III!3,II!1,Y1197~O).HRG(EGFL!3) -> ErbB2(II!1).ErbB3(I_III!3,II!1,Y1197~P).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O P take all branches, once each, in any order⬇ Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).ErbB3(I_III!3,II!1,Y1222~O).HRG(EGFL!3) -> ErbB2(II!1).ErbB3(I_III!3,II!1,Y1222~P).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O P take all branches, once each, in any order⬇ Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).ErbB3(I_III!3,II!1,Y1260~O).HRG(EGFL!3) -> ErbB2(II!1).ErbB3(I_III!3,II!1,Y1260~P).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O P take all branches, once each, in any order⬇ Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).ErbB3(I_III!3,II!1,Y1276~O).HRG(EGFL!3) -> ErbB2(II!1).ErbB3(I_III!3,II!1,Y1276~P).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O P take all branches, once each, in any order⬇ Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).ErbB3(I_III!3,II!1,Y1289~O).HRG(EGFL!3) -> ErbB2(II!1).ErbB3(I_III!3,II!1,Y1289~P).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O P take all branches, once each, in any order⬇ Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).ErbB3(I_III!3,II!1,Y1328~O).HRG(EGFL!3) -> ErbB2(II!1).ErbB3(I_III!3,II!1,Y1328~P).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O P take all branches, once each, in any order⬇ loc M ?En HRG EGFL deg F ?T loc Ex ?En

(ErbB4-ErbB3 dimers) cross-phosphorylation of Erbb3 by ErbB4 at
(1054,1197,1222,Y1260,1276,1289,1328)

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1054~O).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1054~P).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB3 I_III II Y1054 O P take all branches, once each, in any order⬇ Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1197~O).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1197~P).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O P take all branches, once each, in any order⬇ Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1222~O).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1222~P).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O P take all branches, once each, in any order⬇ Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1260~O).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1260~P).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O P take all branches, once each, in any order⬇ Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1276~O).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1276~P).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O P take all branches, once each, in any order⬇ Y1289 O ?P Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1289~O).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1289~P).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O P take all branches, once each, in any order⬇ Y1328 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1328~O).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB3(I_III!3,II!1,Y1328~P).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O P take all branches, once each, in any order⬇ loc M ?En HRG EGFL deg F ?T loc Ex ?En

cross-phosphorylation of ErbB4
(EGFR-ErbB4 dimers) cross-phosphorylation of ErbB4 by EGFR at
(1056,1188,1242)

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB4(I_III!3,II!1,Y1056~O).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB4(I_III!3,II!1,Y1056~P).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB4 I_III II Y1056 O P take all branches, once each, in any order⬇ Y1188 O ?P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB4(I_III!3,II!1,Y1188~O).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB4(I_III!3,II!1,Y1188~P).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB4 I_III II Y1056 O ?P Y1188 O P take all branches, once each, in any order⬇ Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB4(I_III!3,II!1,Y1242~O).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).ErbB4(I_III!3,II!1,Y1242~P).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O P take all branches, once each, in any order⬇ loc M ?En HRG EGFL deg F ?T loc Ex ?En

(ErbB2-ErbB4 dimers) cross-phosphorylation of ErbB4 by ErbB2 at
(1056,1188,1242)

ErbB2(II!1).ErbB4(I_III!3,II!1,Y1056~O).HRG(EGFL!3) -> ErbB2(II!1).ErbB4(I_III!3,II!1,Y1056~P).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ErbB4 I_III II Y1056 O P take all branches, once each, in any order⬇ Y1188 O ?P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).ErbB4(I_III!3,II!1,Y1188~O).HRG(EGFL!3) -> ErbB2(II!1).ErbB4(I_III!3,II!1,Y1188~P).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ErbB4 I_III II Y1056 O ?P Y1188 O P take all branches, once each, in any order⬇ Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).ErbB4(I_III!3,II!1,Y1242~O).HRG(EGFL!3) -> ErbB2(II!1).ErbB4(I_III!3,II!1,Y1242~P).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O P take all branches, once each, in any order⬇ loc M ?En HRG EGFL deg F ?T loc Ex ?En

(ErbB4-ErbB4 dimers) cross-phosphorylation of ErbB4 by ErbB4 at
(1056,1188,1242)

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB4(I_III!3,II!1,Y1056~O).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB4(I_III!3,II!1,Y1056~P).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB4 I_III II Y1056 O P take all branches, once each, in any order⬇ Y1188 O ?P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB4(I_III!3,II!1,Y1188~O).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB4(I_III!3,II!1,Y1188~P).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB4 I_III II Y1056 O ?P Y1188 O P take all branches, once each, in any order⬇ Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB4(I_III!3,II!1,Y1242~O).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).ErbB4(I_III!3,II!1,Y1242~P).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O P take all branches, once each, in any order⬇ loc M ?En HRG EGFL deg F ?T loc Ex ?En

############# INTRINSIC RECEPTOR DEPHOSPHORYLATION ##############
EGFR (992,1068,1086,1114,1148,1173)

EGFR(Y992~P) -> EGFR(Y992~O)

EGFR ?I_III ?II T669 O ?P Y992 O P take one or more branches, once each, in any order⬆ Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

EGFR(Y1068~P) -> EGFR(Y1068~O)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O P take one or more branches, once each, in any order⬆ Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

EGFR(Y1086~P) -> EGFR(Y1086~O)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O P take one or more branches, once each, in any order⬆ Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

EGFR(Y1114~P) -> EGFR(Y1114~O)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O P take one or more branches, once each, in any order⬆ Y1148 O ?P Y1173 O ?P loc M ?En

EGFR(Y1148~P) -> EGFR(Y1148~O)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O P take one or more branches, once each, in any order⬆ Y1173 O ?P loc M ?En

EGFR(Y1173~P) -> EGFR(Y1173~O)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O P take one or more branches, once each, in any order⬆ loc M ?En

ErbB2 (1139,1196,1222,1248)

ErbB2(Y1139~P) -> ErbB2(Y1139~O)

ErbB2 ?II Y1139 O P take one or more branches, once each, in any order⬆ Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

ErbB2(Y1196~P) -> ErbB2(Y1196~O)

ErbB2 ?II Y1139 O ?P Y1196 O P take one or more branches, once each, in any order⬆ Y1222 O ?P Y1248 O ?P loc M ?En

ErbB2(Y1222~P) -> ErbB2(Y1222~O)

ErbB2 ?II Y1139 O ?P Y1196 O ?P Y1222 O P take one or more branches, once each, in any order⬆ Y1248 O ?P loc M ?En

ErbB2(Y1248~P) -> ErbB2(Y1248~O)

ErbB2 ?II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O P take one or more branches, once each, in any order⬆ loc M ?En

ErbB3 (1054,1197,1222,Y1260,1276,1289,1328)

ErbB3(Y1054~P) -> ErbB3(Y1054~O)

ErbB3 ?I_III ?II Y1054 O P take one or more branches, once each, in any order⬆ Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

ErbB3(Y1197~P) -> ErbB3(Y1197~O)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O P take one or more branches, once each, in any order⬆ Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

ErbB3(Y1222~P) -> ErbB3(Y1222~O)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O P take one or more branches, once each, in any order⬆ Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

ErbB3(Y1260~P) -> ErbB3(Y1260~O)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O P take one or more branches, once each, in any order⬆ Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

ErbB3(Y1276~P) -> ErbB3(Y1276~O)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O P take one or more branches, once each, in any order⬆ Y1289 O ?P Y1328 O ?P loc M ?En

ErbB3(Y1289~P) -> ErbB3(Y1289~O)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O P take one or more branches, once each, in any order⬆ Y1328 O ?P loc M ?En

ErbB3(Y1328~P) -> ErbB3(Y1328~O)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O P take one or more branches, once each, in any order⬆ loc M ?En

ErbB3 (1056,1188,1242)

ErbB4(Y1056~P) -> ErbB4(Y1056~O)

ErbB4 ?I_III ?II Y1056 O P take one or more branches, once each, in any order⬆ Y1188 O ?P Y1242 O ?P loc M ?En

ErbB4(Y1188~P) -> ErbB4(Y1188~O)

ErbB4 ?I_III ?II Y1056 O ?P Y1188 O P take one or more branches, once each, in any order⬆ Y1242 O ?P loc M ?En

ErbB4(Y1242~P) -> ErbB4(Y1242~O)

ErbB4 ?I_III ?II Y1056 O ?P Y1188 O ?P Y1242 O P take one or more branches, once each, in any order⬆ loc M ?En

############# Grb2 BINDING TO A RECEPTOR ##############
# EGFR = 1068,1114,1148,1173
# ErbB2 = 1139
EGFR
Y1068,Y1086,Y1148,Y1173

EGFR(Y1068~P) + Grb2(SH2r,SH2s) <-> EGFR(Y1068~P!1).Grb2(SH2r!1,SH2s)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 ⬇⬆P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ⬇⬆ Grb2 ⬇⬆SH2r SH2s ?cSH3 ?nSH3 loc ?C

EGFR(Y1114~P) + Grb2(SH2r,SH2s) <-> EGFR(Y1114~P!1).Grb2(SH2r!1,SH2s)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 ⬇⬆P Y1148 O ?P Y1173 O ?P loc M ?En ⬇⬆ Grb2 ⬇⬆SH2r SH2s ?cSH3 ?nSH3 loc ?C

EGFR(Y1148~P) + Grb2(SH2r,SH2s) <-> EGFR(Y1148~P!1).Grb2(SH2r!1,SH2s)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 ⬇⬆P Y1173 O ?P loc M ?En ⬇⬆ Grb2 ⬇⬆SH2r SH2s ?cSH3 ?nSH3 loc ?C

EGFR(Y1173~P) + Grb2(SH2r,SH2s) <-> EGFR(Y1173~P!1).Grb2(SH2r!1,SH2s)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 ⬇⬆P loc M ?En ⬇⬆ Grb2 ⬇⬆SH2r SH2s ?cSH3 ?nSH3 loc ?C

ErbB2
Y1139

ErbB2(Y1139~P) + Grb2(SH2r,SH2s) <-> ErbB2(Y1139~P!1).Grb2(SH2r!1,SH2s)

ErbB2 ?II Y1139 ⬇⬆P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En ⬇⬆ Grb2 ⬇⬆SH2r SH2s ?cSH3 ?nSH3 loc ?C

############# Shc BINDING TO A RECEPTOR ##############
# EGFR - 992,1086,1114
# ErbB2 - 1196,1222,1248
# ErbB3 - 1328
# ErbB4 - 1188,1242
EGFR
Y992,Y086,Y1114

EGFR(Y992~P) + p52Shc1(PTB) <-> EGFR(Y992~P!1).p52Shc1(PTB!1)

EGFR ?I_III ?II T669 O ?P Y992 ⬇⬆P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ⬇⬆ p52Shc1 ⬇⬆PTB Y317 O ?P loc ?C

EGFR(Y1086~P) + p52Shc1(PTB) <-> EGFR(Y1086~P!1).p52Shc1(PTB!1)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 ⬇⬆P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En ⬇⬆ p52Shc1 ⬇⬆PTB Y317 O ?P loc ?C

EGFR(Y1114~P) + p52Shc1(PTB) <-> EGFR(Y1114~P!1).p52Shc1(PTB!1)

EGFR ?I_III ?II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 ⬇⬆P Y1148 O ?P Y1173 O ?P loc M ?En ⬇⬆ p52Shc1 ⬇⬆PTB Y317 O ?P loc ?C

ErbB2
Y1196,Y1222,Y1248

ErbB2(Y1196~P) + p52Shc1(PTB) <-> ErbB2(Y1196~P!1).p52Shc1(PTB!1)

ErbB2 ?II Y1139 O ?P Y1196 ⬇⬆P Y1222 O ?P Y1248 O ?P loc M ?En ⬇⬆ p52Shc1 ⬇⬆PTB Y317 O ?P loc ?C

ErbB2(Y1222~P) + p52Shc1(PTB) <-> ErbB2(Y1222~P!1).p52Shc1(PTB!1)

ErbB2 ?II Y1139 O ?P Y1196 O ?P Y1222 ⬇⬆P Y1248 O ?P loc M ?En ⬇⬆ p52Shc1 ⬇⬆PTB Y317 O ?P loc ?C

ErbB2(Y1248~P) + p52Shc1(PTB) <-> ErbB2(Y1248~P!1).p52Shc1(PTB!1)

ErbB2 ?II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 ⬇⬆P loc M ?En ⬇⬆ p52Shc1 ⬇⬆PTB Y317 O ?P loc ?C

ErbB3
Y1328

ErbB3(Y1328~P) + p52Shc1(PTB) <-> ErbB3(Y1328~P!1).p52Shc1(PTB!1)

ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 ⬇⬆P loc M ?En ⬇⬆ p52Shc1 ⬇⬆PTB Y317 O ?P loc ?C

ErbB4
Y1188,Y1242

ErbB4(Y1188~P) + p52Shc1(PTB) <-> ErbB4(Y1188~P!1).p52Shc1(PTB!1)

ErbB4 ?I_III ?II Y1056 O ?P Y1188 ⬇⬆P Y1242 O ?P loc M ?En ⬇⬆ p52Shc1 ⬇⬆PTB Y317 O ?P loc ?C

ErbB4(Y1242~P) + p52Shc1(PTB) <-> ErbB4(Y1242~P!1).p52Shc1(PTB!1)

ErbB4 ?I_III ?II Y1056 O ?P Y1188 O ?P Y1242 ⬇⬆P loc M ?En ⬇⬆ p52Shc1 ⬇⬆PTB Y317 O ?P loc ?C

Transphosphorylation of Shc by a receptor
EGFR-EGFR where EGFR transphosphorylates Shc
Y992,Y086,Y1114

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~O,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~P,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~O,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~P,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~O,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~P,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGFR-ErbB2 where EGFR transphosphorylates Shc
Y1196,Y1222,Y1248

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~O,PTB!4).ErbB2(II!1,Y1196~P!4) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~P,PTB!4).ErbB2(II!1,Y1196~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB2 II Y1139 O ?P Y1196 P Y1222 O ?P Y1248 O ?P loc M ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~O,PTB!4).ErbB2(II!1,Y1222~P!4) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~P,PTB!4).ErbB2(II!1,Y1222~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 P Y1248 O ?P loc M ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~O,PTB!4).ErbB2(II!1,Y1248~P!4) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~P,PTB!4).ErbB2(II!1,Y1248~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 P loc M ?En

EGFR-ErbB3 where EGFR transphosphorylates Shc
Y1328

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~O,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~P,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGFR-ErbB4 where EGFR transphosphorylates Shc
Y1188,Y1242

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~O,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~P,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~O,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> EGF(EGFL!2).EGFR(I_III!2,II!1,T669~O).p52Shc1(Y317~P,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2-EGFR where ErbB2 transphosphorylates Shc
Y992,Y086,Y1114

ErbB2(II!1).p52Shc1(Y317~O,PTB!4).EGFR(I_III!2,II!1,Y992~P!4).EGF(EGFL!2) -> ErbB2(II!1).p52Shc1(Y317~P,PTB!4).EGFR(I_III!2,II!1,Y992~P!4).EGF(EGFL!2)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).p52Shc1(Y317~O,PTB!4).EGFR(I_III!2,II!1,Y1086~P!4).EGF(EGFL!2) -> ErbB2(II!1).p52Shc1(Y317~P,PTB!4).EGFR(I_III!2,II!1,Y1086~P!4).EGF(EGFL!2)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).p52Shc1(Y317~O,PTB!4).EGFR(I_III!2,II!1,Y1114~P!4).EGF(EGFL!2) -> ErbB2(II!1).p52Shc1(Y317~P,PTB!4).EGFR(I_III!2,II!1,Y1114~P!4).EGF(EGFL!2)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2-ErbB3 where ErbB2 transphosphorylates Shc
Y1328

ErbB2(II!1).p52Shc1(Y317~O,PTB!4).ErbB3(I_III!2,II!1,Y1328~P!4).HRG(EGFL!2) -> ErbB2(II!1).p52Shc1(Y317~P,PTB!4).ErbB3(I_III!2,II!1,Y1328~P!4).HRG(EGFL!2)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2-ErbB4 where ErbB2 transphosphorylates Shc
Y1188,Y1242

ErbB2(II!1).p52Shc1(Y317~O,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> ErbB2(II!1).p52Shc1(Y317~P,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).p52Shc1(Y317~O,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> ErbB2(II!1).p52Shc1(Y317~P,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB4-EGFR where ErbB4 transphosphorylates Shc
Y086,Y1114

HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~O,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~P,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~O,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~P,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~O,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~P,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB4-ErbB2 where ErbB4 transphosphorylates Shc
Y1196,Y1222,Y1248

HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~O,PTB!4).ErbB2(II!1,Y1196~P!4) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~P,PTB!4).ErbB2(II!1,Y1196~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB2 II Y1139 O ?P Y1196 P Y1222 O ?P Y1248 O ?P loc M ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~O,PTB!4).ErbB2(II!1,Y1222~P!4) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~P,PTB!4).ErbB2(II!1,Y1222~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 P Y1248 O ?P loc M ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~O,PTB!4).ErbB2(II!1,Y1248~P!4) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~P,PTB!4).ErbB2(II!1,Y1248~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 P loc M ?En

ErbB4-ErbB3 where ErbB4 transphosphorylates Shc
Y1328

HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~O,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~P,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB4-ErbB4 where ErbB4 transphosphorylates Shc
Y1188,Y1242

HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~O,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~P,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~O,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> HRG(EGFL!2).ErbB4(I_III!2,II!1).p52Shc1(Y317~P,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En p52Shc1 PTB Y317 O P take all branches, once each, in any order⬇ loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

Intrinsic dephosphorylation of Phospho-Shc

p52Shc1(Y317~P) -> p52Shc1(Y317~O)

p52Shc1 ?PTB Y317 O P take one or more branches, once each, in any order⬆ loc ?C

############# SCAFFOLDING REACTIONS ##############
# These are general reactions of getting from Receptor to RAS via Sos1
Grb2 binds to Shc

Grb2(SH2r,SH2s) + p52Shc1(Y317~P) <-> Grb2(SH2r,SH2s!1).p52Shc1(Y317~P!1)

Grb2 SH2r ⬇⬆SH2s ?cSH3 ?nSH3 loc ?C ⬇⬆ p52Shc1 ?PTB Y317 ⬇⬆P loc ?C

Sos1 binds Grb2

Sos1(PRS) + Grb2(nSH3,cSH3) <-> Sos1(PRS!1).Grb2(nSH3!1,cSH3)

Sos1 ⬇⬆PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 O ?P S1193 O ?P loc ?C ⬇⬆ Grb2 ?SH2r ?SH2s cSH3 ⬇⬆nSH3 loc ?C

NOTE: this reaction's rate is increased to demonstrate positive feedback from the AKT pathway to the Erk pathway
Binding of Sos1 to Gab1-Grb2

Sos1(PRS) + Grb2(nSH3,cSH3!2).Gab1(PRS1_PRS2!2) <-> Sos1(PRS!1).Grb2(nSH3!1,cSH3!2).Gab1(PRS1_PRS2!2)

Sos1 ⬇⬆PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 O ?P S1193 O ?P loc ?C ⬇⬆ Grb2 ?SH2r ?SH2s cSH3 ⬇⬆nSH3 loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

############# KRAS RECRUITEMENT TO RECEPTOR ##############
Binding of KRas to receptor bound Sos1-Grb2-rec at the GEF domain

Sos1(PRS!2,GEF,S1132~O,S1167~O,S1178~O,S1193~O).Grb2(nSH3!2,SH2r!+) + KRas(GTPase,g~GDP) -> Sos1(PRS!2,GEF!3,S1132~O,S1167~O,S1178~O,S1193~O).Grb2(nSH3!2,SH2r!+).KRas(GTPase!3,g~GDP)

Sos1 PRS ?REM ⬇GEF S1132 O S1167 O S1178 O S1193 O loc ?C Grb2 SH2r ?SH2s ?cSH3 nSH3 loc ?C ⬇ KRas ⬇GTPase g GDP loc ?M

Binding of KRas to membrane bound Sos1-Grb2-Shc-rec at the GEF domain

Sos1(PRS!2,GEF,S1132~O,S1167~O,S1178~O,S1193~O).Grb2(nSH3!2,SH2s!1).p52Shc1(PTB!+,Y317~P!1) + KRas(GTPase,g~GDP) -> Sos1(PRS!2,GEF!3,S1132~O,S1167~O,S1178~O,S1193~O).Grb2(nSH3!2,SH2s!1).p52Shc1(PTB!+,Y317~P!1).KRas(GTPase!3,g~GDP)

Sos1 PRS ?REM ⬇GEF S1132 O S1167 O S1178 O S1193 O loc ?C Grb2 ?SH2r SH2s ?cSH3 nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ⬇ KRas ⬇GTPase g GDP loc ?M

Binding of KRas to membrane bound Sos1-Grb2-rec at the REM domain

Sos1(PRS!2,REM,S1132~O,S1167~O,S1178~O,S1193~O).Grb2(nSH3!2,SH2r!+) + KRas(GTPase,g~GTP) -> Sos1(PRS!2,REM!3,S1132~O,S1167~O,S1178~O,S1193~O).Grb2(nSH3!2,SH2r!+).KRas(GTPase!3,g~GTP)

Sos1 PRS ⬇REM ?GEF S1132 O S1167 O S1178 O S1193 O loc ?C Grb2 SH2r ?SH2s ?cSH3 nSH3 loc ?C ⬇ KRas ⬇GTPase g GTP loc ?M

Binding of KRas to membrane bound Sos1-Grb2-Shc-rec at the REM domain

Sos1(PRS!2,REM,S1132~O,S1167~O,S1178~O,S1193~O).Grb2(nSH3!2,SH2s!1).p52Shc1(PTB!+,Y317~P!1) + KRas(GTPase,g~GTP) -> Sos1(PRS!2,REM!3,S1132~O,S1167~O,S1178~O,S1193~O).Grb2(nSH3!2,SH2s!1).p52Shc1(PTB!+,Y317~P!1).KRas(GTPase!3,g~GTP)

Sos1 PRS ⬇REM ?GEF S1132 O S1167 O S1178 O S1193 O loc ?C Grb2 ?SH2r SH2s ?cSH3 nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ⬇ KRas ⬇GTPase g GTP loc ?M

Ras activation by Sos
REM domain unbound

Sos1(REM,GEF!3,S1132~O,S1167~O,S1178~O,S1193~O).KRas(GTPase!3,g~GDP) <-> Sos1(REM,GEF!3,S1132~O,S1167~O,S1178~O,S1193~O).KRas(GTPase!3,g~GTP)

Sos1 ?PRS REM GEF S1132 O S1167 O S1178 O S1193 O loc ?C KRas GTPase g GDP GTP take all branches, once each, in any order⬇⬆ loc ?M

Ras activation by Sos
REM domain bound to Ras-GTP, this is a positive feedback loop which increases Ras activation

Sos1(REM!+,GEF!3,S1132~O,S1167~O,S1178~O,S1193~O).KRas(GTPase!3,g~GDP) <-> Sos1(REM!+,GEF!3,S1132~O,S1167~O,S1178~O,S1193~O).KRas(GTPase!3,g~GTP)

Sos1 ?PRS REM GEF S1132 O S1167 O S1178 O S1193 O loc ?C KRas GTPase g GDP GTP take all branches, once each, in any order⬇⬆ loc ?M

Intrinsic deactivation of Ras

KRas(GTPase,g~GTP) -> KRas(GTPase,g~GDP)

KRas GTPase g GDP GTP take one or more branches, once each, in any order⬆ loc ?M

Dissociation of KRas from Sos1
at GEF domain

Sos1(GEF!3).KRas(GTPase!3) -> Sos1(GEF) + KRas(GTPase)

Sos1 ?PRS ?REM ⬆GEF S1132 O ?P S1167 O ?P S1178 O ?P S1193 O ?P loc ?C ⬆ KRas ⬆GTPase g GDP ?GTP loc ?M

at REM domain

Sos1(REM!3).KRas(GTPase!3) -> Sos1(REM) + KRas(GTPase)

Sos1 ?PRS ⬆REM ?GEF S1132 O ?P S1167 O ?P S1178 O ?P S1193 O ?P loc ?C ⬆ KRas ⬆GTPase g GDP ?GTP loc ?M

############# MAP Kinase Cascade ##############
Activated RAS (RAS-GTP) binds Raf1

KRas(g~GTP,GTPase) + Raf1(RBD) -> KRas(g~GTP,GTPase!1).Raf1(RBD!1)

KRas ⬇GTPase g GTP loc ?M ⬇ Raf1 ⬇RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Activation of Raf1 bound to Ras

KRas(GTPase!1,g~GTP).Raf1(RBD!1,S296~O) -> KRas(GTPase!1,g~GTP).Raf1(RBD!1,S296~P)

KRas GTPase g GTP loc ?M Raf1 RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O P take all branches, once each, in any order⬇ S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

KRas(GTPase!1,g~GTP).Raf1(RBD!1,S338~O) -> KRas(GTPase!1,g~GTP).Raf1(RBD!1,S338~P)

KRas GTPase g GTP loc ?M Raf1 RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O P take all branches, once each, in any order⬇ Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

KRas(GTPase!1,g~GTP).Raf1(RBD!1,Y341~O) -> KRas(GTPase!1,g~GTP).Raf1(RBD!1,Y341~P)

KRas GTPase g GTP loc ?M Raf1 RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O P take all branches, once each, in any order⬇ S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

KRas(GTPase!1,g~GTP).Raf1(RBD!1,T491~O) -> KRas(GTPase!1,g~GTP).Raf1(RBD!1,T491~P)

KRas GTPase g GTP loc ?M Raf1 RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O P take all branches, once each, in any order⬇ S494 O ?P S642 O ?P loc ?C

KRas(GTPase!1,g~GTP).Raf1(RBD!1,S494~O) -> KRas(GTPase!1,g~GTP).Raf1(RBD!1,S494~P)

KRas GTPase g GTP loc ?M Raf1 RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O P take all branches, once each, in any order⬇ S642 O ?P loc ?C

Dissociation of activated Raf1 (MKKK) from Raf1-RAS Complex

Raf1(RBD!1).KRas(GTPase!1) -> Raf1(RBD) + KRas(GTPase)

Raf1 ⬆RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C ⬆ KRas ⬆GTPase g GDP ?GTP loc ?M

## Raf1 intrinsic dephosphorylation of activation sites

Raf1(S296~P) -> Raf1(S296~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O P take one or more branches, once each, in any order⬆ S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1(S338~P) -> Raf1(S338~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O P take one or more branches, once each, in any order⬆ Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1(Y341~P) -> Raf1(Y341~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O P take one or more branches, once each, in any order⬆ S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1(T491~P) -> Raf1(T491~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O P take one or more branches, once each, in any order⬆ S494 O ?P S642 O ?P loc ?C

Raf1(S494~P) -> Raf1(S494~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O P take one or more branches, once each, in any order⬆ S642 O ?P loc ?C

## Raf1 activates MEK1
Activated Raf1 binds to MEK1

Raf1(STkinase,S29~O,S43~O,S259~O!?,S289~O,S296~P,S301~O,S338~P,Y341~P,S471~O,T491~P,S494~P,S642~O) + MEK1(S218~O) -> Raf1(STkinase!1,S29~O,S43~O,S259~O!?,S289~O,S296~P,S301~O,S338~P,Y341~P,S471~O,T491~P,S494~P,S642~O).MEK1(S218~O!1)

Raf1 ?RBD ⬇STkinase S29 O S43 O S259 ?O S289 O S296 P S301 O S338 P Y341 P S471 O T491 P S494 P S642 O loc ?C ⬇ MEK1 ?delta S218 ⬇O S222 O ?P T292 O ?P loc ?C

Raf1(STkinase,S29~O,S43~O,S259~O!?,S289~O,S296~P,S301~O,S338~P,Y341~P,S471~O,T491~P,S494~P,S642~O) + MEK1(S222~O) -> Raf1(STkinase!1,S29~O,S43~O,S259~O!?,S289~O,S296~P,S301~O,S338~P,Y341~P,S471~O,T491~P,S494~P,S642~O).MEK1(S222~O!1)

Raf1 ?RBD ⬇STkinase S29 O S43 O S259 ?O S289 O S296 P S301 O S338 P Y341 P S471 O T491 P S494 P S642 O loc ?C ⬇ MEK1 ?delta S218 O ?P S222 ⬇O T292 O ?P loc ?C

Activated Raf1 activates Mek1

Raf1(STkinase!1,S29~O,S43~O,S259~O!?,S289~O,S296~P,S301~O,S338~P,Y341~P,S471~O,T491~P,S494~P,S642~O).MEK1(S218~O!1) -> Raf1(STkinase!1,S29~O,S43~O,S259~O!?,S289~O,S296~P,S301~O,S338~P,Y341~P,S471~O,T491~P,S494~P,S642~O).MEK1(S218~P!1)

Raf1 ?RBD STkinase S29 O S43 O S259 ?O S289 O S296 P S301 O S338 P Y341 P S471 O T491 P S494 P S642 O loc ?C MEK1 ?delta S218 O P take all branches, once each, in any order⬇ S222 O ?P T292 O ?P loc ?C

Raf1(STkinase!1,S29~O,S43~O,S259~O!?,S289~O,S296~P,S301~O,S338~P,Y341~P,S471~O,T491~P,S494~P,S642~O).MEK1(S222~O!1) -> Raf1(STkinase!1,S29~O,S43~O,S259~O!?,S289~O,S296~P,S301~O,S338~P,Y341~P,S471~O,T491~P,S494~P,S642~O).MEK1(S222~P!1)

Raf1 ?RBD STkinase S29 O S43 O S259 ?O S289 O S296 P S301 O S338 P Y341 P S471 O T491 P S494 P S642 O loc ?C MEK1 ?delta S218 O ?P S222 O P take all branches, once each, in any order⬇ T292 O ?P loc ?C

Raf1-Mek Dissociation

Raf1(STkinase!1).MEK1(S218!1) -> Raf1(STkinase) + MEK1(S218)

Raf1 ?RBD ⬆STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C ⬆ MEK1 ?delta ⬆S218 S222 O ?P T292 O ?P loc ?C

Raf1(STkinase!1).MEK1(S222!1) -> Raf1(STkinase) + MEK1(S222)

Raf1 ?RBD ⬆STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C ⬆ MEK1 ?delta S218 O ?P ⬆S222 T292 O ?P loc ?C

## MEK1 intrinsic dephosphorylation of activation sites

MEK1(S218~P) -> MEK1(S218~O)

MEK1 ?delta S218 O P take one or more branches, once each, in any order⬆ S222 O ?P T292 O ?P loc ?C

MEK1(S222~P) -> MEK1(S222~O)

MEK1 ?delta S218 O ?P S222 O P take one or more branches, once each, in any order⬆ T292 O ?P loc ?C

## MEK1 activates ERK2
Activated MEK1 binds to ERK2

MEK1(delta,S218~P!?,S222~P!?,T292~O) + ERK2(CD,STkinase) -> MEK1(delta!1,S218~P!?,S222~P!?,T292~O).ERK2(CD!1,STkinase)

MEK1 ⬇delta S218 ?P S222 ?P T292 O loc ?C ⬇ ERK2 ⬇CD STkinase T185 O ?P Y187 O ?P loc ?C

Activated Mek1 phosphorylates Erk2

ERK2(CD!1,T185~O).MEK1(delta!1,S218~P!?,S222~P!?,T292~O) -> ERK2(CD!1,T185~P).MEK1(delta!1,S218~P!?,S222~P!?,T292~O)

ERK2 CD ?STkinase T185 O P take all branches, once each, in any order⬇ Y187 O ?P loc ?C MEK1 delta S218 ?P S222 ?P T292 O loc ?C

ERK2(CD!1,Y187~O).MEK1(delta!1,S218~P!?,S222~P!?,T292~O) -> ERK2(CD!1,Y187~P).MEK1(delta!1,S218~P!?,S222~P!?,T292~O)

ERK2 CD ?STkinase T185 O ?P Y187 O P take all branches, once each, in any order⬇ loc ?C MEK1 delta S218 ?P S222 ?P T292 O loc ?C

Dissociation of ERK2 from MEK1

ERK2(CD!1).MEK1(delta!1) -> ERK2(CD) + MEK1(delta)

ERK2 ⬆CD ?STkinase T185 O ?P Y187 O ?P loc ?C ⬆ MEK1 ⬆delta S218 O ?P S222 O ?P T292 O ?P loc ?C

# ERK2 dephosphorylation

ERK2(Y187~P) -> ERK2(Y187~O)

ERK2 ?CD ?STkinase T185 O ?P Y187 O P take one or more branches, once each, in any order⬆ loc ?C

ERK2(T185~P) -> ERK2(T185~O)

ERK2 ?CD ?STkinase T185 O P take one or more branches, once each, in any order⬆ Y187 O ?P loc ?C

############# ERK2'S NEGATIVE FEEDBACK LOOPS ##############
# Erk2 inhibits Sos1, EGFR, Raf1, and Mek
BINDING
Activated ERK2 binds with Sos1

ERK2(STkinase,CD,T185~P,Y187~P) + Sos1(S1132~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).Sos1(S1132~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Sos1 ?PRS ?REM ?GEF S1132 ⬇O S1167 O ?P S1178 O ?P S1193 O ?P loc ?C

ERK2(STkinase,CD,T185~P,Y187~P) + Sos1(S1167~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).Sos1(S1167~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 ⬇O S1178 O ?P S1193 O ?P loc ?C

ERK2(STkinase,CD,T185~P,Y187~P) + Sos1(S1178~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).Sos1(S1178~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 ⬇O S1193 O ?P loc ?C

ERK2(STkinase,CD,T185~P,Y187~P) + Sos1(S1193~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).Sos1(S1193~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 O ?P S1193 ⬇O loc ?C

ERK2 binds with EGFR

ERK2(STkinase,CD,T185~P,Y187~P) + EGFR(T669~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).EGFR(T669~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ EGFR ?I_III ?II T669 ⬇O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

ERK2 Binds to Raf1-1

ERK2(STkinase,CD,T185~P,Y187~P) + Raf1(S29~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).Raf1(S29~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Raf1 ?RBD ?STkinase S29 ⬇O S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase,CD,T185~P,Y187~P) + Raf1(S43~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).Raf1(S43~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Raf1 ?RBD ?STkinase S29 O ?P S43 ⬇O S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase,CD,T185~P,Y187~P) + Raf1(S289~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).Raf1(S289~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 ⬇O S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase,CD,T185~P,Y187~P) + Raf1(S301~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).Raf1(S301~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 ⬇O S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase,CD,T185~P,Y187~P) + Raf1(S471~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).Raf1(S471~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 ⬇O T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase,CD,T185~P,Y187~P) + Raf1(S642~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).Raf1(S642~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 ⬇O loc ?C

ERK2 Binds to MEK1

ERK2(STkinase,CD,T185~P,Y187~P) + MEK1(T292~O) -> ERK2(STkinase!1,CD,T185~P,Y187~P).MEK1(T292~O!1)

ERK2 CD ⬇STkinase T185 P Y187 P loc ?C ⬇ MEK1 ?delta S218 O ?P S222 O ?P T292 ⬇O loc ?C

ERK2 inhibits Sos1

ERK2(STkinase!1,T185~P,Y187~P).Sos1(S1132~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Sos1(S1132~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Sos1 ?PRS ?REM ?GEF S1132 O P take all branches, once each, in any order⬇ S1167 O ?P S1178 O ?P S1193 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Sos1(S1167~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Sos1(S1167~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O P take all branches, once each, in any order⬇ S1178 O ?P S1193 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Sos1(S1178~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Sos1(S1178~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 O P take all branches, once each, in any order⬇ S1193 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Sos1(S1193~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Sos1(S1193~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 O ?P S1193 O P take all branches, once each, in any order⬇ loc ?C

ERK2 inhibits EGFR dimers.

ERK2(STkinase!1,T185~P,Y187~P).EGFR(T669~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).EGFR(T669~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C EGFR ?I_III ?II T669 O P take all branches, once each, in any order⬇ Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

ERK2 inhibits Raf1-1

ERK2(STkinase!1,T185~P,Y187~P).Raf1(S29~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Raf1(S29~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Raf1 ?RBD ?STkinase S29 O P take all branches, once each, in any order⬇ S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Raf1(S43~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Raf1(S43~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Raf1 ?RBD ?STkinase S29 O ?P S43 O P take all branches, once each, in any order⬇ S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Raf1(S289~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Raf1(S289~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O P take all branches, once each, in any order⬇ S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Raf1(S301~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Raf1(S301~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O P take all branches, once each, in any order⬇ S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Raf1(S471~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Raf1(S471~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O P take all branches, once each, in any order⬇ T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Raf1(S642~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Raf1(S642~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O P take all branches, once each, in any order⬇ loc ?C

ERK2 inhibits MEK1.

ERK2(STkinase!1,T185~P,Y187~P).MEK1(T292~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).MEK1(T292~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C MEK1 ?delta S218 O ?P S222 O ?P T292 O P take all branches, once each, in any order⬇ loc ?C

inhibitory sites intrinsic dephosphorylation
Sos1 sites

Sos1(S1132~P) -> Sos1(S1132~O)

Sos1 ?PRS ?REM ?GEF S1132 O P take one or more branches, once each, in any order⬆ S1167 O ?P S1178 O ?P S1193 O ?P loc ?C

Sos1(S1167~P) -> Sos1(S1167~O)

Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O P take one or more branches, once each, in any order⬆ S1178 O ?P S1193 O ?P loc ?C

Sos1(S1178~P) -> Sos1(S1178~O)

Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 O P take one or more branches, once each, in any order⬆ S1193 O ?P loc ?C

Sos1(S1193~P) -> Sos1(S1193~O)

Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 O ?P S1193 O P take one or more branches, once each, in any order⬆ loc ?C

EGFR site

EGFR(T669~P) -> EGFR(T669~O)

EGFR ?I_III ?II T669 O P take one or more branches, once each, in any order⬆ Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

Raf1 sites

Raf1(S29~P) -> Raf1(S29~O)

Raf1 ?RBD ?STkinase S29 O P take one or more branches, once each, in any order⬆ S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1(S43~P) -> Raf1(S43~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O P take one or more branches, once each, in any order⬆ S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1(S289~P) -> Raf1(S289~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O P take one or more branches, once each, in any order⬆ S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1(S301~P) -> Raf1(S301~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O P take one or more branches, once each, in any order⬆ S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1(S471~P) -> Raf1(S471~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O P take one or more branches, once each, in any order⬆ T491 O ?P S494 O ?P S642 O ?P loc ?C

Raf1(S642~P) -> Raf1(S642~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O P take one or more branches, once each, in any order⬆ loc ?C

Mek site

MEK1(T292~P) -> MEK1(T292~O)

MEK1 ?delta S218 O ?P S222 O ?P T292 O P take one or more branches, once each, in any order⬆ loc ?C

ERK2 regulatory complex Dissociation
Erk dissasociates with Sos1

ERK2(STkinase!1).Sos1(S1132!1) -> ERK2(STkinase) + Sos1(S1132)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Sos1 ?PRS ?REM ?GEF ⬆S1132 S1167 O ?P S1178 O ?P S1193 O ?P loc ?C

ERK2(STkinase!1).Sos1(S1167!1) -> ERK2(STkinase) + Sos1(S1167)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Sos1 ?PRS ?REM ?GEF S1132 O ?P ⬆S1167 S1178 O ?P S1193 O ?P loc ?C

ERK2(STkinase!1).Sos1(S1178!1) -> ERK2(STkinase) + Sos1(S1178)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O ?P ⬆S1178 S1193 O ?P loc ?C

ERK2(STkinase!1).Sos1(S1193!1) -> ERK2(STkinase) + Sos1(S1193)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Sos1 ?PRS ?REM ?GEF S1132 O ?P S1167 O ?P S1178 O ?P ⬆S1193 loc ?C

Erk dissasociates with EGFR

ERK2(STkinase!1).EGFR(T669!1) -> ERK2(STkinase) + EGFR(T669)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ EGFR ?I_III ?II ⬆T669 Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

Erk dissasociates with Raf1

ERK2(STkinase!1).Raf1(S29!1) -> ERK2(STkinase) + Raf1(S29)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Raf1 ?RBD ?STkinase ⬆S29 S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase!1).Raf1(S43!1) -> ERK2(STkinase) + Raf1(S43)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Raf1 ?RBD ?STkinase S29 O ?P ⬆S43 S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase!1).Raf1(S289!1) -> ERK2(STkinase) + Raf1(S289)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P ⬆S289 S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase!1).Raf1(S301!1) -> ERK2(STkinase) + Raf1(S301)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P ⬆S301 S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase!1).Raf1(S471!1) -> ERK2(STkinase) + Raf1(S471)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P ⬆S471 T491 O ?P S494 O ?P S642 O ?P loc ?C

ERK2(STkinase!1).Raf1(S642!1) -> ERK2(STkinase) + Raf1(S642)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O ?P S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P ⬆S642 loc ?C

Erk dissasociates with MEK1

ERK2(STkinase!1).MEK1(T292!1) -> ERK2(STkinase) + MEK1(T292)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ MEK1 ?delta S218 O ?P S222 O ?P ⬆T292 loc ?C

############# Gab1 interactions ##############
Gab1 binds to membrane localized Grb2 (Grb2-p52Shc1-rec)

Gab1(PRS1_PRS2) + Grb2(cSH3,SH2s!2).p52Shc1(Y317~P!2,PTB!+) -> Gab1(PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+)

Gab1 ?PH ⬇PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C ⬇ Grb2 ?SH2r SH2s ⬇cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C

Gab1 binds to membrane localized Grb2 (Grb2-rec)

Gab1(PRS1_PRS2) + Grb2(cSH3,SH2r!+) -> Gab1(PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+)

Gab1 ?PH ⬇PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C ⬇ Grb2 SH2r ?SH2s ⬇cSH3 ?nSH3 loc ?C

Transphosphorylation of Gab1 by a receptor
EGFR-EGFR where EGFR transphosphorylates Gab1-Grb2-Shc

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGFR-EGFR where EGFR transphosphorylates Gab1-Grb2

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

EGFR-ErbB2 where EGFR transphosphorylates Gab1-Grb2-Shc

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 P Y1222 O ?P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 P Y1222 O ?P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 P Y1222 O ?P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 P Y1222 O ?P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 P loc M ?En

EGFR-ErbB2 where EGFR transphosphorylates Gab1-Grb2

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ErbB2 II Y1139 P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ErbB2 II Y1139 P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ErbB2 II Y1139 P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ErbB2 II Y1139 P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

EGFR-ErbB3 where EGFR transphosphorylates Gab1-Grb2-Shc

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGFR-ErbB4 where EGFR transphosphorylates Gab1-Grb2-Shc

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> EGF(EGFL!5).EGFR(I_III!5,II!1,T669~O).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

EGF EGFL deg F ?T loc Ex ?En EGFR I_III II T669 O Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2-EGFR where ErbB2 transphosphorylates Gab1-Grb2-Shc

ErbB2(II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2-EGFR where ErbB2 transphosphorylates Gab1-Grb2

ErbB2(II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> ErbB2(II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB2-ErbB3 where ErbB2 transphosphorylates Gab1-Grb2-Shc

ErbB2(II!1).Gab1(Y447~O,PRS1_PRS2!5).Grb2(cSH3!5,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y447~P,PRS1_PRS2!5).Grb2(cSH3!5,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y472~O,PRS1_PRS2!5).Grb2(cSH3!5,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y472~P,PRS1_PRS2!5).Grb2(cSH3!5,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y619~O,PRS1_PRS2!5).Grb2(cSH3!5,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y619~P,PRS1_PRS2!5).Grb2(cSH3!5,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y657~O,PRS1_PRS2!5).Grb2(cSH3!5,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y657~P,PRS1_PRS2!5).Grb2(cSH3!5,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2-ErbB4 where ErbB2 transphosphorylates Gab1-Grb2-Shc

ErbB2(II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB2(II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> ErbB2(II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

Transphosphorylation of Gab1 by a receptor
ErbB4-EGFR where ErbB4 transphosphorylates Gab1-Grb2-Shc

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y992~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1086~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB4-EGFR where ErbB4 transphosphorylates Gab1-Grb2

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1068~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1114~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 P Y1148 O ?P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1148~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 P Y1173 O ?P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).EGFR(I_III!3,II!1,Y1173~P!4).EGF(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C EGFR I_III II T669 O ?P Y992 O ?P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 P loc M ?En EGF EGFL deg F ?T loc Ex ?En

ErbB4-ErbB2 where ErbB4 transphosphorylates Gab1-Grb2-Shc

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 P Y1222 O ?P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 P Y1222 O ?P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 P Y1222 O ?P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1196~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 P Y1222 O ?P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1222~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB2(II!1,Y1248~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB2 II Y1139 O ?P Y1196 O ?P Y1222 O ?P Y1248 P loc M ?En

ErbB4-ErbB2 where ErbB4 transphosphorylates Gab1-Grb2

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ErbB2 II Y1139 P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ErbB2 II Y1139 P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ErbB2 II Y1139 P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2r!4).ErbB2(II!1,Y1139~P!4)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ErbB2 II Y1139 P Y1196 O ?P Y1222 O ?P Y1248 O ?P loc M ?En

ErbB4-ErbB3 where ErbB4 transphosphorylates Gab1-Grb2-Shc

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB3(I_III!3,II!1,Y1328~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB3 I_III II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

ErbB4-ErbB4 where ErbB4 transphosphorylates Gab1-Grb2-Shc

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1188~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 P Y1242 O ?P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y447~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take all branches, once each, in any order⬇ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y472~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take all branches, once each, in any order⬇ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y619~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take all branches, once each, in any order⬇ Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~O,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3) -> HRG(EGFL!5).ErbB4(I_III!5,II!1).Gab1(Y657~P,PRS1_PRS2!6).Grb2(cSH3!6,SH2s!2).p52Shc1(Y317~P!2,PTB!4).ErbB4(I_III!3,II!1,Y1242~P!4).HRG(EGFL!3)

HRG EGFL deg F ?T loc Ex ?En ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 O ?P loc M ?En Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take all branches, once each, in any order⬇ loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ErbB4 I_III II Y1056 O ?P Y1188 O ?P Y1242 P loc M ?En HRG EGFL deg F ?T loc Ex ?En

Gab1 Dissociation

Gab1(PRS1_PRS2!1).Grb2(cSH3!1) -> Gab1(PRS1_PRS2) + Grb2(cSH3)

Gab1 ?PH ⬆PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C ⬆ Grb2 ?SH2r ?SH2s ⬆cSH3 ?nSH3 loc ?C

Phospho Erk and Gab1 interaction
ERK2 binds with Gab1

ERK2(STkinase,T185~P,Y187~P) + Gab1(T312~O) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(T312~O!1)

ERK2 ?CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Gab1 ?PH ?PRS1_PRS2 T312 ⬇O S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase,T185~P,Y187~P) + Gab1(S381~O) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(S381~O!1)

ERK2 ?CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 ⬇O Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase,T185~P,Y187~P) + Gab1(S454~O) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(S454~O!1)

ERK2 ?CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 ⬇O Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase,T185~P,Y187~P) + Gab1(T476~O) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(T476~O!1)

ERK2 ?CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 ⬇O S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase,T185~P,Y187~P) + Gab1(S581~O) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(S581~O!1)

ERK2 ?CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 ⬇O S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase,T185~P,Y187~P) + Gab1(S597~O) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(S597~O!1)

ERK2 ?CD ⬇STkinase T185 P Y187 P loc ?C ⬇ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 ⬇O Y619 O ?P Y657 O ?P loc ?C

ERK2 phosphorylates Gab1

ERK2(STkinase!1,T185~P,Y187~P).Gab1(T312~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(T312~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Gab1 ?PH ?PRS1_PRS2 T312 O P take all branches, once each, in any order⬇ S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Gab1(S381~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(S381~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O P take all branches, once each, in any order⬇ Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Gab1(S454~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(S454~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O P take all branches, once each, in any order⬇ Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Gab1(T476~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(T476~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O P take all branches, once each, in any order⬇ S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Gab1(S581~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(S581~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O P take all branches, once each, in any order⬇ S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase!1,T185~P,Y187~P).Gab1(S597~O!1) -> ERK2(STkinase!1,T185~P,Y187~P).Gab1(S597~P!1)

ERK2 ?CD STkinase T185 P Y187 P loc ?C Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O P take all branches, once each, in any order⬇ Y619 O ?P Y657 O ?P loc ?C

Dissociation of ERK2 and phospho Gab1

ERK2(STkinase!1).Gab1(T312!1) -> ERK2(STkinase) + Gab1(T312)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Gab1 ?PH ?PRS1_PRS2 ⬆T312 S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase!1).Gab1(S381!1) -> ERK2(STkinase) + Gab1(S381)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Gab1 ?PH ?PRS1_PRS2 T312 O ?P ⬆S381 Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase!1).Gab1(S454!1) -> ERK2(STkinase) + Gab1(S454)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P ⬆S454 Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase!1).Gab1(T476!1) -> ERK2(STkinase) + Gab1(T476)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P ⬆T476 S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase!1).Gab1(S581!1) -> ERK2(STkinase) + Gab1(S581)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P ⬆S581 S597 O ?P Y619 O ?P Y657 O ?P loc ?C

ERK2(STkinase!1).Gab1(S597!1) -> ERK2(STkinase) + Gab1(S597)

ERK2 ?CD ⬆STkinase T185 O ?P Y187 O ?P loc ?C ⬆ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P ⬆S597 Y619 O ?P Y657 O ?P loc ?C

Intrinsic dephosphorylation of receptor phosphorylated Gab1 sites

Gab1(Y447~P) -> Gab1(Y447~O)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O P take one or more branches, once each, in any order⬆ S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1(Y472~P) -> Gab1(Y472~O)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O P take one or more branches, once each, in any order⬆ T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1(Y619~P) -> Gab1(Y619~O)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O P take one or more branches, once each, in any order⬆ Y657 O ?P loc ?C

Gab1(Y657~P) -> Gab1(Y657~O)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O P take one or more branches, once each, in any order⬆ loc ?C

Intrinsic dephosphorylation of Erk2 phosphorylated Gab1 sites

Gab1(T312~P) -> Gab1(T312~O)

Gab1 ?PH ?PRS1_PRS2 T312 O P take one or more branches, once each, in any order⬆ S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1(S381~P) -> Gab1(S381~O)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O P take one or more branches, once each, in any order⬆ Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1(S454~P) -> Gab1(S454~O)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O P take one or more branches, once each, in any order⬆ Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1(T476~P) -> Gab1(T476~O)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O P take one or more branches, once each, in any order⬆ S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1(S581~P) -> Gab1(S581~O)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O P take one or more branches, once each, in any order⬆ S597 O ?P Y619 O ?P Y657 O ?P loc ?C

Gab1(S597~P) -> Gab1(S597~O)

Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O P take one or more branches, once each, in any order⬆ Y619 O ?P Y657 O ?P loc ?C

Gab1 binding to PIP3

Gab1(PH,PRS1_PRS2,S581~P) + PIP3(C3P,two~F) -> Gab1(PH!1,PRS1_PRS2,S581~P).PIP3(C3P!1,two~F)

Gab1 ⬇PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 P S597 O ?P Y619 O ?P Y657 O ?P loc ?C ⬇ PIP3 ⬇C3P two F loc ?M

Gab1(PH!1).PIP3(C3P!1) -> Gab1(PH) + PIP3(C3P)

Gab1 ⬆PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C ⬆ PIP3 ⬆C3P two F ?T loc ?M

############# PI3K interactions ##############
PI3K binds membrane localized Gab1-Grb2-Shc and Gab1-Grb2 at Y447,Y472, and Y619
Y447

PI3K(G_p85_nSH2_cSH2,R_p85_nSH2_cSH2) + Gab1(Y447~P,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~O!2,PTB!+) -> PI3K(G_p85_nSH2_cSH2!3,R_p85_nSH2_cSH2).Gab1(Y447~P!3,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~O!2,PTB!+)

PI3K ?lipid_kinase R_p85_nSH2_cSH2 ⬇G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇ Gab1 ?PH PRS1_PRS2 T312 ?O S381 ?O Y447 ⬇P S454 ?O Y472 O ?P T476 ?O S581 ?O S597 ?O Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 O loc ?C

PI3K(G_p85_nSH2_cSH2,R_p85_nSH2_cSH2) + Gab1(Y447~P,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+) -> PI3K(G_p85_nSH2_cSH2!2,R_p85_nSH2_cSH2).Gab1(Y447~P!2,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+)

PI3K ?lipid_kinase R_p85_nSH2_cSH2 ⬇G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇ Gab1 ?PH PRS1_PRS2 T312 ?O S381 ?O Y447 ⬇P S454 ?O Y472 O ?P T476 ?O S581 ?O S597 ?O Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C

Y472

PI3K(G_p85_nSH2_cSH2,R_p85_nSH2_cSH2) + Gab1(Y472~P,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~O!2,PTB!+) -> PI3K(G_p85_nSH2_cSH2!3,R_p85_nSH2_cSH2).Gab1(Y472~P!3,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~O!2,PTB!+)

PI3K ?lipid_kinase R_p85_nSH2_cSH2 ⬇G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇ Gab1 ?PH PRS1_PRS2 T312 ?O S381 ?O Y447 O ?P S454 ?O Y472 ⬇P T476 ?O S581 ?O S597 ?O Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 O loc ?C

PI3K(G_p85_nSH2_cSH2,R_p85_nSH2_cSH2) + Gab1(Y472~P,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+) -> PI3K(G_p85_nSH2_cSH2!2,R_p85_nSH2_cSH2).Gab1(Y472~P!2,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+)

PI3K ?lipid_kinase R_p85_nSH2_cSH2 ⬇G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇ Gab1 ?PH PRS1_PRS2 T312 ?O S381 ?O Y447 O ?P S454 ?O Y472 ⬇P T476 ?O S581 ?O S597 ?O Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C

Y619

PI3K(G_p85_nSH2_cSH2,R_p85_nSH2_cSH2) + Gab1(Y619~P,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~O!2,PTB!+) -> PI3K(G_p85_nSH2_cSH2!3,R_p85_nSH2_cSH2).Gab1(Y619~P!3,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~O!2,PTB!+)

PI3K ?lipid_kinase R_p85_nSH2_cSH2 ⬇G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇ Gab1 ?PH PRS1_PRS2 T312 ?O S381 ?O Y447 O ?P S454 ?O Y472 O ?P T476 ?O S581 ?O S597 ?O Y619 ⬇P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 O loc ?C

PI3K(G_p85_nSH2_cSH2,R_p85_nSH2_cSH2) + Gab1(Y619~P,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+) -> PI3K(G_p85_nSH2_cSH2!2,R_p85_nSH2_cSH2).Gab1(Y619~P!2,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+)

PI3K ?lipid_kinase R_p85_nSH2_cSH2 ⬇G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇ Gab1 ?PH PRS1_PRS2 T312 ?O S381 ?O Y447 O ?P S454 ?O Y472 O ?P T476 ?O S581 ?O S597 ?O Y619 ⬇P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C

PI3K binds membrane localized Gab1-PIP3

PI3K(G_p85_nSH2_cSH2,R_p85_nSH2_cSH2) + Gab1(PH!1,Y447~P,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?).PIP3(C3P!1) -> PI3K(G_p85_nSH2_cSH2!2,R_p85_nSH2_cSH2).Gab1(PH!1,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,Y447~P!2).PIP3(C3P!1)

PI3K ?lipid_kinase R_p85_nSH2_cSH2 ⬇G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇ Gab1 PH ?PRS1_PRS2 T312 ?O S381 ?O Y447 ⬇P S454 ?O Y472 O ?P T476 ?O S581 ?O S597 ?O Y619 O ?P Y657 O ?P loc ?C PIP3 C3P two F ?T loc ?M

PI3K(G_p85_nSH2_cSH2,R_p85_nSH2_cSH2) + Gab1(PH!1,Y472~P,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?).PIP3(C3P!1) -> PI3K(G_p85_nSH2_cSH2!2,R_p85_nSH2_cSH2).Gab1(PH!1,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,Y472~P!2).PIP3(C3P!1)

PI3K ?lipid_kinase R_p85_nSH2_cSH2 ⬇G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇ Gab1 PH ?PRS1_PRS2 T312 ?O S381 ?O Y447 O ?P S454 ?O Y472 ⬇P T476 ?O S581 ?O S597 ?O Y619 O ?P Y657 O ?P loc ?C PIP3 C3P two F ?T loc ?M

PI3K(G_p85_nSH2_cSH2,R_p85_nSH2_cSH2) + Gab1(PH!1,Y619~P,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?).PIP3(C3P!1) -> PI3K(G_p85_nSH2_cSH2!2,R_p85_nSH2_cSH2).Gab1(PH!1,T312~O!?,S381~O!?,S454~O!?,T476~O!?,S581~O!?,S597~O!?,Y619~P!2).PIP3(C3P!1)

PI3K ?lipid_kinase R_p85_nSH2_cSH2 ⬇G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇ Gab1 PH ?PRS1_PRS2 T312 ?O S381 ?O Y447 O ?P S454 ?O Y472 O ?P T476 ?O S581 ?O S597 ?O Y619 ⬇P Y657 O ?P loc ?C PIP3 C3P two F ?T loc ?M

PI3K dissasociation from Gab1

PI3K(G_p85_nSH2_cSH2!1).Gab1(Y447!1) -> PI3K(G_p85_nSH2_cSH2) + Gab1(Y447)

PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 ⬆G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬆ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P ⬆Y447 S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

PI3K(G_p85_nSH2_cSH2!1).Gab1(Y472!1) -> PI3K(G_p85_nSH2_cSH2) + Gab1(Y472)

PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 ⬆G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬆ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P ⬆Y472 T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

PI3K(G_p85_nSH2_cSH2!1).Gab1(Y619!1) -> PI3K(G_p85_nSH2_cSH2) + Gab1(Y619)

PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 ⬆G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬆ Gab1 ?PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P ⬆Y619 Y657 O ?P loc ?C

membrane bound PI3K Binding to active Ras

PI3K(p110_RBD,G_p85_nSH2_cSH2!3).Gab1(Y447~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+) + KRas(g~GTP,GTPase) -> PI3K(p110_RBD!4,G_p85_nSH2_cSH2!3).Gab1(Y447~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+).KRas(g~GTP,GTPase!4)

PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ⬇p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ⬇ KRas ⬇GTPase g GTP loc ?M

PI3K(p110_RBD,G_p85_nSH2_cSH2!2).Gab1(Y447~P!2,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+) + KRas(g~GTP,GTPase) -> PI3K(G_p85_nSH2_cSH2!2,p110_RBD!4).Gab1(Y447~P!2,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+).KRas(g~GTP,GTPase!4)

PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ⬇p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ⬇ KRas ⬇GTPase g GTP loc ?M

PI3K(p110_RBD,G_p85_nSH2_cSH2!3).Gab1(Y472~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+) + KRas(g~GTP,GTPase) -> PI3K(p110_RBD!4,G_p85_nSH2_cSH2!3).Gab1(Y472~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+).KRas(g~GTP,GTPase!4)

PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ⬇p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ⬇ KRas ⬇GTPase g GTP loc ?M

PI3K(p110_RBD,G_p85_nSH2_cSH2!2).Gab1(Y472~P!2,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+) + KRas(g~GTP,GTPase) -> PI3K(G_p85_nSH2_cSH2!2,p110_RBD!4).Gab1(Y472~P!2,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+).KRas(g~GTP,GTPase!4)

PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ⬇p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ⬇ KRas ⬇GTPase g GTP loc ?M

PI3K(p110_RBD,G_p85_nSH2_cSH2!3).Gab1(Y619~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+) + KRas(g~GTP,GTPase) -> PI3K(p110_RBD!4,G_p85_nSH2_cSH2!3).Gab1(Y619~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+).KRas(g~GTP,GTPase!4)

PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ⬇p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C ⬇ KRas ⬇GTPase g GTP loc ?M

PI3K(p110_RBD,G_p85_nSH2_cSH2!2).Gab1(Y619~P!2,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+) + KRas(g~GTP,GTPase) -> PI3K(G_p85_nSH2_cSH2!2,p110_RBD!4).Gab1(Y619~P!2,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+).KRas(g~GTP,GTPase!4)

PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ⬇p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C ⬇ KRas ⬇GTPase g GTP loc ?M

PI3K Dissociation from Ras

PI3K(p110_RBD!1).KRas(GTPase!1) -> PI3K(p110_RBD) + KRas(GTPase)

PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 ?G_p85_nSH2_cSH2 ⬆p110_RBD loc ?C ⬆ KRas ⬆GTPase g GDP ?GTP loc ?M

PI3K binds to ErbB3

PI3K(R_p85_nSH2_cSH2,G_p85_nSH2_cSH2) + ErbB3(Y1054~P) <-> PI3K(R_p85_nSH2_cSH2!1,G_p85_nSH2_cSH2).ErbB3(Y1054~P!1)

PI3K ?lipid_kinase ⬇⬆R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇⬆ ErbB3 ?I_III ?II Y1054 ⬇⬆P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

PI3K(R_p85_nSH2_cSH2,G_p85_nSH2_cSH2) + ErbB3(Y1197~P) <-> PI3K(R_p85_nSH2_cSH2!1,G_p85_nSH2_cSH2).ErbB3(Y1197~P!1)

PI3K ?lipid_kinase ⬇⬆R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇⬆ ErbB3 ?I_III ?II Y1054 O ?P Y1197 ⬇⬆P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

PI3K(R_p85_nSH2_cSH2,G_p85_nSH2_cSH2) + ErbB3(Y1222~P) <-> PI3K(R_p85_nSH2_cSH2!1,G_p85_nSH2_cSH2).ErbB3(Y1222~P!1)

PI3K ?lipid_kinase ⬇⬆R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇⬆ ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 ⬇⬆P Y1260 O ?P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

PI3K(R_p85_nSH2_cSH2,G_p85_nSH2_cSH2) + ErbB3(Y1260~P) <-> PI3K(R_p85_nSH2_cSH2!1,G_p85_nSH2_cSH2).ErbB3(Y1260~P!1)

PI3K ?lipid_kinase ⬇⬆R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇⬆ ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 ⬇⬆P Y1276 O ?P Y1289 O ?P Y1328 O ?P loc M ?En

PI3K(R_p85_nSH2_cSH2,G_p85_nSH2_cSH2) + ErbB3(Y1276~P) <-> PI3K(R_p85_nSH2_cSH2!1,G_p85_nSH2_cSH2).ErbB3(Y1276~P!1)

PI3K ?lipid_kinase ⬇⬆R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇⬆ ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 ⬇⬆P Y1289 O ?P Y1328 O ?P loc M ?En

PI3K(R_p85_nSH2_cSH2,G_p85_nSH2_cSH2) + ErbB3(Y1289~P) <-> PI3K(R_p85_nSH2_cSH2!1,G_p85_nSH2_cSH2).ErbB3(Y1289~P!1)

PI3K ?lipid_kinase ⬇⬆R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇⬆ ErbB3 ?I_III ?II Y1054 O ?P Y1197 O ?P Y1222 O ?P Y1260 O ?P Y1276 O ?P Y1289 ⬇⬆P Y1328 O ?P loc M ?En

PI3K binds to ErbB4

PI3K(R_p85_nSH2_cSH2,G_p85_nSH2_cSH2) + ErbB4(Y1056~P) <-> PI3K(R_p85_nSH2_cSH2!1,G_p85_nSH2_cSH2).ErbB4(Y1056~P!1)

PI3K ?lipid_kinase ⬇⬆R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C ⬇⬆ ErbB4 ?I_III ?II Y1056 ⬇⬆P Y1188 O ?P Y1242 O ?P loc M ?En

############# PIP3 interactions ##############
creation of PIP3 by active PI3K-Gab1~rec

PI3K(G_p85_nSH2_cSH2!3).Gab1(Y447~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3).Gab1(Y447~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C Gab1 PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C

PI3K(G_p85_nSH2_cSH2!3).Gab1(Y472~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3).Gab1(Y472~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C Gab1 PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C

PI3K(G_p85_nSH2_cSH2!3).Gab1(Y619~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3).Gab1(Y619~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C Gab1 PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C

PI3K(G_p85_nSH2_cSH2!3).Gab1(Y447~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2r!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3).Gab1(Y447~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2r!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C Gab1 PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C

PI3K(G_p85_nSH2_cSH2!3).Gab1(Y472~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2r!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3).Gab1(Y472~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2r!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C Gab1 PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C

PI3K(G_p85_nSH2_cSH2!3).Gab1(Y619~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2r!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3).Gab1(Y619~P!3,PRS1_PRS2!1,PH).Grb2(cSH3!1,SH2r!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C Gab1 PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C

With PI3K bound to Ras

PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y447~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y447~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C

PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y472~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y472~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C

PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y619~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y619~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2s!2).p52Shc1(Y317~P!2,PTB!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 P Y657 O ?P loc ?C Grb2 ?SH2r SH2s cSH3 ?nSH3 loc ?C p52Shc1 PTB Y317 P loc ?C

PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y447~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y447~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C

PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y472~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y472~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C

PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y619~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!3,p110_RBD!+).Gab1(Y619~P!3,PRS1_PRS2!1).Grb2(cSH3!1,SH2r!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc ?C Gab1 ?PH PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 P Y657 O ?P loc ?C Grb2 SH2r ?SH2s cSH3 ?nSH3 loc ?C

creation of PIP3 by PI3k-Gab1-PIP3

PI3K(G_p85_nSH2_cSH2!1).Gab1(Y447~P!1,PH!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!1).Gab1(Y447~P!1,PH!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C Gab1 PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

PI3K(G_p85_nSH2_cSH2!1).Gab1(Y472~P!1,PH!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!1).Gab1(Y472~P!1,PH!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C Gab1 PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 P T476 O ?P S581 O ?P S597 O ?P Y619 O ?P Y657 O ?P loc ?C

PI3K(G_p85_nSH2_cSH2!1).Gab1(Y619~P!1,PH!+) -> PIP3(C3P,two~F,loc~M) + PI3K(G_p85_nSH2_cSH2!1).Gab1(Y619~P!1,PH!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase ?R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 ?p110_RBD loc ?C Gab1 PH ?PRS1_PRS2 T312 O ?P S381 O ?P Y447 O ?P S454 O ?P Y472 O ?P T476 O ?P S581 O ?P S597 O ?P Y619 P Y657 O ?P loc ?C

creation of PIP3 by PI3K-ErbB3

PI3K(R_p85_nSH2_cSH2!+) -> PIP3(C3P,two~F,loc~M) + PI3K(R_p85_nSH2_cSH2!+)

PIP3 C3P two F loc M synthesized PI3K ?lipid_kinase R_p85_nSH2_cSH2 ?G_p85_nSH2_cSH2 ?p110_RBD loc ?C

PIP3 dephosphorylation

PIP3(C3P,two~F) -> PIP3(C3P,two~T)

PIP3 C3P two F T take all branches, once each, in any order⬇ loc ?M

############# AKT and CDK1 interactions ##############
Akt1 binding to PIP3

Akt1(PH) + PIP3(C3P,two~F) <-> Akt1(PH!1).PIP3(C3P!1,two~F)

Akt1 ⬇⬆PH ?STkinase T308 O ?P S473 O ?P loc ?C ⬇⬆ PIP3 ⬇⬆C3P two F loc ?M

PDK1 binding to PIP3

PDK1(PH) + PIP3(C3P,two~F) <-> PDK1(PH!1).PIP3(C3P!1,two~F)

PDK1 ⬇⬆PH ?STkinase loc ?C ⬇⬆ PIP3 ⬇⬆C3P two F loc ?M

PDK1-PIP3 binds to AKT-PIP3

PDK1(PH!+,STkinase) + Akt1(PH!+,T308~O) -> PDK1(PH!+,STkinase!1).Akt1(PH!+,T308~O!1)

PDK1 PH ⬇STkinase loc ?C ⬇ Akt1 PH ?STkinase T308 ⬇O S473 O ?P loc ?C

phosphorylation of AKT-PIP3 by CDK1-PIP3

PDK1(PH!+,STkinase!1).Akt1(PH!+,T308~O!1) -> PDK1(PH!+,STkinase!1).Akt1(PH!+,T308~P!1)

PDK1 PH STkinase loc ?C Akt1 PH ?STkinase T308 O P take all branches, once each, in any order⬇ S473 O ?P loc ?C

PDK1(STkinase!1).Akt1(T308!1) -> PDK1(STkinase) + Akt1(T308)

PDK1 ?PH ⬆STkinase loc ?C ⬆ Akt1 ?PH ?STkinase ⬆T308 S473 O ?P loc ?C

Phosphorylation of S473 by an unknown kinase, this only occurs when T308 is phosphorylated

Akt1(T308~P!?,S473~O) -> Akt1(T308~P!?,S473~P)

Akt1 ?PH ?STkinase T308 ?P S473 O P take all branches, once each, in any order⬇ loc ?C

Activated Akt-1 phosphorylates Raf-1 at S259
This is an inhibitory feedback loop from the AKT pathway to the ERK pathway

Akt1(T308~P!?,S473~P,STkinase) + Raf1(S259~O) -> Akt1(T308~P!?,S473~P,STkinase!1).Raf1(S259~O!1)

Akt1 ?PH ⬇STkinase T308 ?P S473 P loc ?C ⬇ Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 ⬇O S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Akt1(T308~P!?,S473~P,STkinase!1).Raf1(S259~O!1) -> Akt1(T308~P!?,S473~P,STkinase!1).Raf1(S259~P!1)

Akt1 ?PH STkinase T308 ?P S473 P loc ?C Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O P take all branches, once each, in any order⬇ S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Akt1(STkinase!1).Raf1(S259!1) -> Akt1(STkinase) + Raf1(S259)

Akt1 ?PH ⬆STkinase T308 O ?P S473 O ?P loc ?C ⬆ Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P ⬆S259 S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Intrinsic dephosphorylation of phosphorylated residues on AKT

Raf1(S259~P) -> Raf1(S259~O)

Raf1 ?RBD ?STkinase S29 O ?P S43 O ?P S259 O P take one or more branches, once each, in any order⬆ S289 O ?P S296 O ?P S301 O ?P S338 O ?P Y341 O ?P S471 O ?P T491 O ?P S494 O ?P S642 O ?P loc ?C

Akt1(T308~P) -> Akt1(T308~O)

Akt1 ?PH ?STkinase T308 O P take one or more branches, once each, in any order⬆ S473 O ?P loc ?C

Akt1(S473~P) -> Akt1(S473~O)

Akt1 ?PH ?STkinase T308 O ?P S473 O P take one or more branches, once each, in any order⬆ loc ?C

############# p120RasGAP interactions ##############

p120RasGAP(nSH2) + EGFR(Y992~P) <-> p120RasGAP(nSH2!1).EGFR(Y992~P!1)

p120RasGAP ⬇⬆nSH2 ?GAP ⬇⬆ EGFR ?I_III ?II T669 O ?P Y992 ⬇⬆P Y1068 O ?P Y1086 O ?P Y1114 O ?P Y1148 O ?P Y1173 O ?P loc M ?En

p120RasGAP(nSH2!+,GAP) + KRas(GTPase,g~GTP) -> p120RasGAP(nSH2!+,GAP!1).KRas(GTPase!1,g~GTP)

p120RasGAP nSH2 ⬇GAP ⬇ KRas ⬇GTPase g GTP loc ?M

p120RasGAP(GAP!1).KRas(GTPase!1,g~GTP) -> p120RasGAP(GAP!1).KRas(GTPase!1,g~GDP)

p120RasGAP ?nSH2 GAP KRas GTPase g GDP GTP take one or more branches, once each, in any order⬆ loc ?M

p120RasGAP(GAP!1).KRas(GTPase!1) -> p120RasGAP(GAP) + KRas(GTPase)

p120RasGAP ?nSH2 ⬆GAP ⬆ KRas ⬆GTPase g GDP ?GTP loc ?M