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

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

EGFR I_III 1II 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 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M

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

EGFR I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M

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

EGFR I_III 1II 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 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M

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

EGFR I_III 1II 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 1II Y1056 O P Y1188 O P Y1242 O P loc M

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

ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M

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

ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M ErbB3 I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M

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

ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M ErbB4 I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M

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

ErbB3 I_III 1II 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 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M

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

ErbB3 I_III 1II 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 1II Y1056 O P Y1188 O P Y1242 O P loc M

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

ErbB4 I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M ErbB4 I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M

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

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

EGFR I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc En ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc En

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

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

EGFR I_III 1II 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 1II Y1056 O P Y1188 O P Y1242 O P loc En

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

ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc En ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc En

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

ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc En ErbB3 I_III 1II 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!1,loc~En).ErbB4(II!1,loc~En)

ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc En ErbB4 I_III 1II Y1056 O P Y1188 O P Y1242 O P loc En

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

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

ErbB3 I_III 1II 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 1II Y1056 O P Y1188 O P Y1242 O P loc En

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

ErbB4 I_III 1II Y1056 O P Y1188 O P Y1242 O P loc En ErbB4 I_III 1II Y1056 O P Y1188 O P Y1242 O P loc En

ERK2(T185~P!?)

ERK2 CD STkinase T185 P Y187 O P loc C

Akt1(S473~P!?)

Akt1 PH STkinase T308 O P S473 P loc C

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(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(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(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(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(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(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(Y1139~P!?)

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

ErbB2(Y1196~P!?)

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

ErbB2(Y1222~P!?)

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

ErbB2(Y1248~P!?)

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

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(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(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(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(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(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(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(Y1056~P!?)

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

ErbB4(Y1188~P!?)

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

ErbB4(Y1242~P!?)

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

p52Shc1(Y317~P!?)

p52Shc1 PTB Y317 P loc C

Sos1(S1132~P!?)

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

Sos1(S1167~P!?)

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

Sos1(S1178~P!?)

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

Sos1(S1193~P!?)

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

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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(S218~P!?)

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

MEK1(S222~P!?)

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

MEK1(T292~P!?)

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

ERK2(Y187~P!?)

ERK2 CD STkinase T185 O P Y187 P loc C

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 1 ⬆⬇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 1 ⬆⬇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 1 ⬆⬇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 1 ⬆⬇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 1 ⬆⬇I_III II Y1056 O P Y1188 O P Y1242 O P loc M HRG 1 ⬆⬇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 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M EGFR 2 ⬆⬇I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M EGF 2 ⬆⬇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 2EGFL deg F loc Ex EGFR 2I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M EGFR 3 ⬆⬇I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M EGF 3 ⬆⬇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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M EGFR 2 ⬆⬇I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M EGF 2 ⬆⬇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 2 ⬆⬇EGFL deg F loc Ex EGFR 2 ⬆⬇I_III 1II 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 1II 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 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M ErbB3 2 ⬆⬇I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M HRG 2 ⬆⬇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 2EGFL deg F loc Ex EGFR 2I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M ErbB3 3 ⬆⬇I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M HRG 3 ⬆⬇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 2 ⬆⬇EGFL deg F loc Ex EGFR 2 ⬆⬇I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M HRG 3EGFL 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 2 ⬆⬇EGFL deg F loc Ex EGFR 2 ⬆⬇I_III 1II 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 1II 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 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M ErbB4 2 ⬆⬇I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M HRG 2 ⬆⬇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 2EGFL deg F loc Ex EGFR 2I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M ErbB4 3 ⬆⬇I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M HRG 3 ⬆⬇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 2 ⬆⬇EGFL deg F loc Ex EGFR 2 ⬆⬇I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M ErbB3 2 ⬆⬇I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M HRG 2 ⬆⬇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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M ErbB4 2 ⬆⬇I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M HRG 2 ⬆⬇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 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M ErbB3 2 ⬆⬇I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M HRG 2 ⬆⬇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 2EGFL deg F loc Ex ErbB3 2I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M ErbB3 3 ⬆⬇I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M HRG 3 ⬆⬇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 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M ErbB4 2 ⬆⬇I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M HRG 2 ⬆⬇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 2 ⬆⬇EGFL deg F loc Ex ErbB3 2 ⬆⬇I_III 1II 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 1II 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 2EGFL deg F loc Ex ErbB3 2I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M ErbB4 3 ⬆⬇I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M HRG 3 ⬆⬇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 2 ⬆⬇EGFL deg F loc Ex ErbB3 2 ⬆⬇I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 O P loc M ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M HRG 3EGFL 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 1II Y1056 O P Y1188 O P Y1242 O P loc M ErbB4 2 ⬆⬇I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M HRG 2 ⬆⬇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 2EGFL deg F loc Ex ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M ErbB4 3 ⬆⬇I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M HRG 3 ⬆⬇EGFL deg F loc Ex
############# RECEPTOR DIMERIZATION ##############EGFR-EGFREGFR-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 1 ⬆⬇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 1 ⬆⬇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 1I_III 2 ⬆⬇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 1EGFL deg F T loc Ex EGFR I_III 2 ⬆⬇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 1I_III 3 ⬆⬇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 1EGFL deg F T loc Ex EGFR 2I_III 3 ⬆⬇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 2EGFL deg F T loc Ex
EGFR-ErbB2EGFR-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 1 ⬆⬇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 1 ⬆⬇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 1I_III 2 ⬆⬇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 1EGFL deg F T loc Ex ErbB2 2 ⬆⬇II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M
EGFR-ErbB3EGFR-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 1 ⬆⬇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 1 ⬆⬇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 1I_III 2 ⬆⬇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 1EGFL deg F T loc Ex ErbB3 I_III 2 ⬆⬇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 1I_III 2 ⬆⬇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 1EGFL deg F T loc Ex EGFR I_III 2 ⬆⬇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 1I_III 3 ⬆⬇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 1EGFL deg F T loc Ex ErbB3 2I_III 3 ⬆⬇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 2EGFL deg F T loc Ex
EGFR-ErbB4EGFR-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 1 ⬆⬇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 1 ⬆⬇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 1I_III 2 ⬆⬇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 1EGFL deg F T loc Ex ErbB4 I_III 2 ⬆⬇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 1I_III 2 ⬆⬇II Y1056 O P Y1188 O P Y1242 O P loc M HRG 1EGFL deg F T loc Ex EGFR I_III 2 ⬆⬇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 1I_III 3 ⬆⬇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 1EGFL deg F T loc Ex ErbB4 2I_III 3 ⬆⬇II Y1056 O P Y1188 O P Y1242 O P loc M HRG 2EGFL 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 1 ⬆⬇II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M ErbB2 1 ⬆⬇II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M
ErbB2-ErbB3ErbB2-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 1 ⬆⬇II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M ErbB3 I_III 1 ⬆⬇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 1I_III 2 ⬆⬇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 1EGFL deg F T loc Ex ErbB2 2 ⬆⬇II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M
ErbB2-ErbB4ErbB2-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 1 ⬆⬇II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M ErbB4 I_III 1 ⬆⬇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 1I_III 2 ⬆⬇II Y1056 O P Y1188 O P Y1242 O P loc M HRG 1EGFL deg F T loc Ex ErbB2 2 ⬆⬇II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M
ErbB3-ErbB3ErbB3-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 1 ⬆⬇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 1 ⬆⬇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 1I_III 2 ⬆⬇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 1EGFL deg F T loc Ex ErbB3 I_III 2 ⬆⬇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 1I_III 3 ⬆⬇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 1EGFL deg F T loc Ex ErbB3 2I_III 3 ⬆⬇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 2EGFL deg F T loc Ex
ErbB3-ErbB4ErbB3-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 1 ⬆⬇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 1 ⬆⬇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 1I_III 2 ⬆⬇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 1EGFL deg F T loc Ex ErbB4 I_III 2 ⬆⬇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 2 ⬆⬇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 1I_III 2 ⬆⬇II Y1056 O P Y1188 O P Y1242 O P loc M HRG 1EGFL 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 1I_III 3 ⬆⬇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 1EGFL deg F T loc Ex ErbB4 2I_III 3 ⬆⬇II Y1056 O P Y1188 O P Y1242 O P loc M HRG 2EGFL deg F T loc Ex
ErbB4-ErbB4ErbB4-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 1 ⬆⬇II Y1056 O P Y1188 O P Y1242 O P loc M ErbB4 I_III 1 ⬆⬇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 1I_III 2 ⬆⬇II Y1056 O P Y1188 O P Y1242 O P loc M HRG 1EGFL deg F T loc Ex ErbB4 I_III 2 ⬆⬇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 1I_III 3 ⬆⬇II Y1056 O P Y1188 O P Y1242 O P loc M HRG 1EGFL deg F T loc Ex ErbB4 2I_III 3 ⬆⬇II Y1056 O P Y1188 O P Y1242 O P loc M HRG 2EGFL deg F T loc Ex
############# RECEPTOR INTERNALIZATION ##############EGFR-EGFREGFR-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 1I_III 3II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ EGFR 2I_III 3II 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 2EGFL 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 1I_III 2II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ EGFR I_III 2II 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 2II 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 2II 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 1I_III 2II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB2 2II 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 2II 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 2II 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 1I_III 3II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB3 2I_III 3II 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 2EGFL 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 3II 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 2I_III 3II 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 2EGFL 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 1I_III 3II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB3 I_III 3II 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 3II 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 3II 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 1I_III 3II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB4 2I_III 3II Y1056 O P Y1188 O P Y1242 O P loc M En take all branches, once each, in any order⬇⬇ HRG 2EGFL 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 3II 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 2I_III 3II Y1056 O P Y1188 O P Y1242 O P loc M En take all branches, once each, in any order⬇⬇ HRG 2EGFL 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 1I_III 3II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB4 I_III 3II 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 3II 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 3II 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En take all branches, once each, in any order⬇⬇ ErbB2 1II 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 1I_III 2II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB2 2II 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 2II 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 2II 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 1I_III 2II Y1056 O P Y1188 O P Y1242 O P loc M En take all branches, once each, in any order⬇⬇ HRG 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB2 2II 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 2II Y1056 O P Y1188 O P Y1242 O P loc M En take all branches, once each, in any order⬇⬇ ErbB2 2II 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 1I_III 2II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB3 3I_III 2II 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 3EGFL 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 1I_III 2II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB3 I_III 2II 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 2II 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 2II 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 1I_III 2II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB4 3I_III 2II Y1056 O P Y1188 O P Y1242 O P loc M En take all branches, once each, in any order⬇⬇ HRG 3EGFL 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 1I_III 2II 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 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB4 I_III 2II 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 2II 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 1I_III 2II Y1056 O P Y1188 O P Y1242 O P loc M En take all branches, once each, in any order⬇⬇ HRG 1EGFL 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 2II 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 2II 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 1I_III 2II Y1056 O P Y1188 O P Y1242 O P loc M En take all branches, once each, in any order⬇⬇ HRG 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB4 3I_III 2II Y1056 O P Y1188 O P Y1242 O P loc M En take all branches, once each, in any order⬇⬇ HRG 3EGFL 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 1I_III 2II Y1056 O P Y1188 O P Y1242 O P loc M En take all branches, once each, in any order⬇⬇ HRG 1EGFL deg F T loc Ex En take all branches, once each, in any order⬇⬇ ErbB4 I_III 2II 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 2II Y1056 O P Y1188 O P Y1242 O P loc M En take all branches, once each, in any order⬇⬇ ErbB4 I_III 2II 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 1 ⬆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 1 ⬆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 1 ⬆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 1 ⬆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 1 ⬆I_III II Y1056 O P Y1188 O P Y1242 O P loc En HRG 1 ⬆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 3 ⬆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 3 ⬆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 2 ⬆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 2 ⬆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 3 ⬆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 3 ⬆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 3 ⬆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 3 ⬆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 2 ⬆II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc En ErbB2 2 ⬆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 2 ⬆II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc En ErbB3 I_III 2 ⬆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 2 ⬆II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc En ErbB4 I_III 2 ⬆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 2 ⬆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 2 ⬆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 2 ⬆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 2 ⬆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 2 ⬆II Y1056 O P Y1188 O P Y1242 O P loc En ErbB4 I_III 2 ⬆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 ReactionsNOTE: 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En EGFR 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB2 1II 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB2 1II 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB2 1II 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB2 1II 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB2 1II 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB2 1II 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB2 1II 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB2 1II 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB3 3I_III 1II 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 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB4 3I_III 1II Y1056 O P take all branches, once each, in any order⬇⬇ Y1188 O P Y1242 O P loc M En HRG 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB4 3I_III 1II Y1056 O P Y1188 O P take all branches, once each, in any order⬇⬇ Y1242 O P loc M En HRG 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 O P take all branches, once each, in any order⬇⬇ loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En ErbB4 3I_III 1II Y1056 O P take all branches, once each, in any order⬇⬇ Y1188 O P Y1242 O P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En ErbB4 3I_III 1II Y1056 O P Y1188 O P take all branches, once each, in any order⬇⬇ Y1242 O P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 O P take all branches, once each, in any order⬇⬇ loc M En HRG 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB4 3I_III 1II Y1056 O P take all branches, once each, in any order⬇⬇ Y1188 O P Y1242 O P loc M En HRG 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB4 3I_III 1II Y1056 O P Y1188 O P take all branches, once each, in any order⬇⬇ Y1242 O P loc M En HRG 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 O P take all branches, once each, in any order⬇⬇ loc M En HRG 3EGFL 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 = 1139EGFRY1068,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 1 ⬆⬇P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En Grb2 1 ⬆⬇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 1 ⬆⬇P Y1148 O P Y1173 O P loc M En Grb2 1 ⬆⬇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 1 ⬆⬇P Y1173 O P loc M En Grb2 1 ⬆⬇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 1 ⬆⬇P loc M En Grb2 1 ⬆⬇SH2r SH2s cSH3 nSH3 loc C
ErbB2Y1139

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

ErbB2 II Y1139 1 ⬆⬇P Y1196 O P Y1222 O P Y1248 O P loc M En Grb2 1 ⬆⬇SH2r SH2s cSH3 nSH3 loc C
############# Shc BINDING TO A RECEPTOR ############### EGFR - 992,1086,1114# ErbB2 - 1196,1222,1248# ErbB3 - 1328# ErbB4 - 1188,1242EGFRY992,Y086,Y1114

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

EGFR I_III II T669 O P Y992 1 ⬆⬇P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 1 ⬆⬇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 1 ⬆⬇P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 1 ⬆⬇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 1 ⬆⬇P Y1148 O P Y1173 O P loc M En p52Shc1 1 ⬆⬇PTB Y317 O P loc C
ErbB2Y1196,Y1222,Y1248

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

ErbB2 II Y1139 O P Y1196 1 ⬆⬇P Y1222 O P Y1248 O P loc M En p52Shc1 1 ⬆⬇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 1 ⬆⬇P Y1248 O P loc M En p52Shc1 1 ⬆⬇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 1 ⬆⬇P loc M En p52Shc1 1 ⬆⬇PTB Y317 O P loc C
ErbB3Y1328

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 1 ⬆⬇P loc M En p52Shc1 1 ⬆⬇PTB Y317 O P loc C
ErbB4Y1188,Y1242

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

ErbB4 I_III II Y1056 O P Y1188 1 ⬆⬇P Y1242 O P loc M En p52Shc1 1 ⬆⬇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 1 ⬆⬇P loc M En p52Shc1 1 ⬆⬇PTB Y317 O P loc C
Transphosphorylation of Shc by a receptorEGFR-EGFR where EGFR transphosphorylates ShcY992,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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL deg F T loc Ex En
EGFR-ErbB2 where EGFR transphosphorylates ShcY1196,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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB2 1II Y1139 O P Y1196 4P 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 4P 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 4P loc M En
EGFR-ErbB3 where EGFR transphosphorylates ShcY1328

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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL deg F T loc Ex En
EGFR-ErbB4 where EGFR transphosphorylates ShcY1188,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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 2EGFL deg F T loc Ex En EGFR 2I_III 1II T669 O Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL deg F T loc Ex En
ErbB2-EGFR where ErbB2 transphosphorylates ShcY992,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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C EGFR 2I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 2EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C EGFR 2I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 2EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C EGFR 2I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 2EGFL deg F T loc Ex En
ErbB2-ErbB3 where ErbB2 transphosphorylates ShcY1328

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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB3 2I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 2EGFL deg F T loc Ex En
ErbB2-ErbB4 where ErbB2 transphosphorylates ShcY1188,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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL deg F T loc Ex En
ErbB4-EGFR where ErbB4 transphosphorylates ShcY086,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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL deg F T loc Ex En
ErbB4-ErbB2 where ErbB4 transphosphorylates ShcY1196,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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB2 1II Y1139 O P Y1196 4P 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 4P 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 4P loc M En
ErbB4-ErbB3 where ErbB4 transphosphorylates ShcY1328

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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL deg F T loc Ex En
ErbB4-ErbB4 where ErbB4 transphosphorylates ShcY1188,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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 2EGFL deg F T loc Ex En ErbB4 2I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En p52Shc1 4PTB Y317 O P take all branches, once each, in any order⬇⬇ loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 Sos1Grb2 binds to Shc

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

Grb2 SH2r 1 ⬆⬇SH2s cSH3 nSH3 loc C p52Shc1 PTB Y317 1 ⬆⬇P loc C
Sos1 binds Grb2

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

Sos1 1 ⬆⬇PRS REM GEF S1132 O P S1167 O P S1178 O P S1193 O P loc C Grb2 SH2r SH2s cSH3 1 ⬆⬇nSH3 loc C
NOTE: this reaction's rate is increased to demonstrate positive feedback from the AKT pathway to the Erk pathwayBinding 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 1 ⬆⬇PRS REM GEF S1132 O P S1167 O P S1178 O P S1193 O P loc C Grb2 SH2r SH2s 2cSH3 1 ⬆⬇nSH3 loc C Gab1 PH 2PRS1_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 2PRS REM 3 ⬇GEF S1132 O S1167 O S1178 O S1193 O loc C Grb2 SH2r SH2s cSH3 2nSH3 loc C KRas 3 ⬇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 2PRS REM 3 ⬇GEF S1132 O S1167 O S1178 O S1193 O loc C Grb2 SH2r 1SH2s cSH3 2nSH3 loc C p52Shc1 PTB Y317 1P loc C KRas 3 ⬇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 2PRS 3 ⬇REM GEF S1132 O S1167 O S1178 O S1193 O loc C Grb2 SH2r SH2s cSH3 2nSH3 loc C KRas 3 ⬇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 2PRS 3 ⬇REM GEF S1132 O S1167 O S1178 O S1193 O loc C Grb2 SH2r 1SH2s cSH3 2nSH3 loc C p52Shc1 PTB Y317 1P loc C KRas 3 ⬇GTPase g GTP loc M
Ras activation by SosREM 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 3GEF S1132 O S1167 O S1178 O S1193 O loc C KRas 3GTPase g GDP GTP take all branches, once each, in any order⬇⬇ loc M
Ras activation by SosREM 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 3GEF S1132 O S1167 O S1178 O S1193 O loc C KRas 3GTPase 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 Sos1at GEF domain

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

Sos1 PRS REM 3 ⬆GEF S1132 O P S1167 O P S1178 O P S1193 O P loc C KRas 3 ⬆GTPase g GDP GTP loc M
at REM domain

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

Sos1 PRS 3 ⬆REM GEF S1132 O P S1167 O P S1178 O P S1193 O P loc C KRas 3 ⬆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 1 ⬇GTPase g GTP loc M Raf1 1 ⬇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 1GTPase g GTP loc M Raf1 1RBD 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 1GTPase g GTP loc M Raf1 1RBD 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 1GTPase g GTP loc M Raf1 1RBD 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 1GTPase g GTP loc M Raf1 1RBD 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 1GTPase g GTP loc M Raf1 1RBD 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 1 ⬆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 1 ⬆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 MEK1Activated 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 1 ⬇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 1 ⬇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 1 ⬇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 1 ⬇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 1STkinase 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 1O 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 1STkinase 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 1O 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 1 ⬆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 1 ⬆S218 S222 O P T292 O P loc C

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

Raf1 RBD 1 ⬆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 1 ⬆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 ERK2Activated 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 1 ⬇delta S218 P S222 P T292 O loc C ERK2 1 ⬇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 1CD STkinase T185 O P take all branches, once each, in any order⬇⬇ Y187 O P loc C MEK1 1delta 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 1CD STkinase T185 O P Y187 O P take all branches, once each, in any order⬇⬇ loc C MEK1 1delta S218 P S222 P T292 O loc C
Dissociation of ERK2 from MEK1

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

ERK2 1 ⬆CD STkinase T185 O P Y187 O P loc C MEK1 1 ⬆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 MekBINDINGActivated 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 1 ⬇STkinase T185 P Y187 P loc C Sos1 PRS REM GEF S1132 1 ⬇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 1 ⬇STkinase T185 P Y187 P loc C Sos1 PRS REM GEF S1132 O P S1167 1 ⬇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 1 ⬇STkinase T185 P Y187 P loc C Sos1 PRS REM GEF S1132 O P S1167 O P S1178 1 ⬇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 1 ⬇STkinase T185 P Y187 P loc C Sos1 PRS REM GEF S1132 O P S1167 O P S1178 O P S1193 1 ⬇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 1 ⬇STkinase T185 P Y187 P loc C EGFR I_III II T669 1 ⬇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 1 ⬇STkinase T185 P Y187 P loc C Raf1 RBD STkinase S29 1 ⬇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 1 ⬇STkinase T185 P Y187 P loc C Raf1 RBD STkinase S29 O P S43 1 ⬇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 1 ⬇STkinase T185 P Y187 P loc C Raf1 RBD STkinase S29 O P S43 O P S259 O P S289 1 ⬇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 1 ⬇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 1 ⬇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 1 ⬇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 1 ⬇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 1 ⬇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 1 ⬇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 1 ⬇STkinase T185 P Y187 P loc C MEK1 delta S218 O P S222 O P T292 1 ⬇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 1STkinase T185 P Y187 P loc C Sos1 PRS REM GEF S1132 1O 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 1STkinase T185 P Y187 P loc C Sos1 PRS REM GEF S1132 O P S1167 1O 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 1STkinase T185 P Y187 P loc C Sos1 PRS REM GEF S1132 O P S1167 O P S1178 1O 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 1STkinase T185 P Y187 P loc C Sos1 PRS REM GEF S1132 O P S1167 O P S1178 O P S1193 1O 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 1STkinase T185 P Y187 P loc C EGFR I_III II T669 1O 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 1STkinase T185 P Y187 P loc C Raf1 RBD STkinase S29 1O 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 1STkinase T185 P Y187 P loc C Raf1 RBD STkinase S29 O P S43 1O 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 1STkinase T185 P Y187 P loc C Raf1 RBD STkinase S29 O P S43 O P S259 O P S289 1O 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 1STkinase 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 1O 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 1STkinase 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 1O 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 1STkinase 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 1O 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 1STkinase T185 P Y187 P loc C MEK1 delta S218 O P S222 O P T292 1O P take all branches, once each, in any order⬇⬇ loc C
inhibitory sites intrinsic dephosphorylationSos1 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 DissociationErk dissasociates with Sos1

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

ERK2 CD 1 ⬆STkinase T185 O P Y187 O P loc C Sos1 PRS REM GEF 1 ⬆S1132 S1167 O P S1178 O P S1193 O P loc C

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

ERK2 CD 1 ⬆STkinase T185 O P Y187 O P loc C Sos1 PRS REM GEF S1132 O P 1 ⬆S1167 S1178 O P S1193 O P loc C

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

ERK2 CD 1 ⬆STkinase T185 O P Y187 O P loc C Sos1 PRS REM GEF S1132 O P S1167 O P 1 ⬆S1178 S1193 O P loc C

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

ERK2 CD 1 ⬆STkinase T185 O P Y187 O P loc C Sos1 PRS REM GEF S1132 O P S1167 O P S1178 O P 1 ⬆S1193 loc C
Erk dissasociates with EGFR

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

ERK2 CD 1 ⬆STkinase T185 O P Y187 O P loc C EGFR I_III II 1 ⬆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 1 ⬆STkinase T185 O P Y187 O P loc C Raf1 RBD STkinase 1 ⬆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 1 ⬆STkinase T185 O P Y187 O P loc C Raf1 RBD STkinase S29 O P 1 ⬆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 1 ⬆STkinase T185 O P Y187 O P loc C Raf1 RBD STkinase S29 O P S43 O P S259 O P 1 ⬆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 1 ⬆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 1 ⬆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 1 ⬆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 1 ⬆S471 T491 O P S494 O P S642 O P loc C

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

ERK2 CD 1 ⬆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 1 ⬆S642 loc C
Erk dissasociates with MEK1

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

ERK2 CD 1 ⬆STkinase T185 O P Y187 O P loc C MEK1 delta S218 O P S222 O P 1 ⬆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 1 ⬇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 2SH2s 1 ⬇cSH3 nSH3 loc C p52Shc1 PTB Y317 2P 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 1 ⬇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 1 ⬇cSH3 nSH3 loc C
Transphosphorylation of Gab1 by a receptorEGFR-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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C ErbB2 1II Y1139 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C ErbB2 1II Y1139 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C ErbB2 1II Y1139 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C ErbB2 1II Y1139 4P 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En EGFR 5I_III 1II 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 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 5PRS1_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 2SH2s 5cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 5PRS1_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 2SH2s 5cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 5PRS1_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 2SH2s 5cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 5PRS1_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 2SH2s 5cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 1II Y1139 O P Y1196 O P Y1222 O P Y1248 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL deg F T loc Ex En
Transphosphorylation of Gab1 by a receptorErbB4-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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 4P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 4P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 4P Y1086 O P Y1114 O P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 4P Y1148 O P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 4P Y1173 O P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C EGFR 3I_III 1II T669 O P Y992 O P Y1068 O P Y1086 O P Y1114 O P Y1148 O P Y1173 4P loc M En EGF 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB2 1II Y1139 O P Y1196 O P Y1222 O P Y1248 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C ErbB2 1II Y1139 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C ErbB2 1II Y1139 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C ErbB2 1II Y1139 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 4SH2r SH2s 6cSH3 nSH3 loc C ErbB2 1II Y1139 4P 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB3 3I_III 1II Y1054 O P Y1197 O P Y1222 O P Y1260 O P Y1276 O P Y1289 O P Y1328 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 4P Y1242 O P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL 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 5EGFL deg F T loc Ex En ErbB4 5I_III 1II Y1056 O P Y1188 O P Y1242 O P loc M En Gab1 PH 6PRS1_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 2SH2s 6cSH3 nSH3 loc C p52Shc1 4PTB Y317 2P loc C ErbB4 3I_III 1II Y1056 O P Y1188 O P Y1242 4P loc M En HRG 3EGFL deg F T loc Ex En
Gab1 Dissociation

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

Gab1 PH 1 ⬆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 1 ⬆cSH3 nSH3 loc C
Phospho Erk and Gab1 interactionERK2 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 1 ⬇STkinase T185 P Y187 P loc C Gab1 PH PRS1_PRS2 T312 1 ⬇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 1 ⬇STkinase T185 P Y187 P loc C Gab1 PH PRS1_PRS2 T312 O P S381 1 ⬇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 1 ⬇STkinase T185 P Y187 P loc C Gab1 PH PRS1_PRS2 T312 O P S381 O P Y447 O P S454 1 ⬇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 1 ⬇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 1 ⬇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 1 ⬇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 1 ⬇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 1 ⬇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 1 ⬇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 1STkinase T185 P Y187 P loc C Gab1 PH PRS1_PRS2 T312 1O 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 1STkinase T185 P Y187 P loc C Gab1 PH PRS1_PRS2 T312 O P S381 1O 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 1STkinase T185 P Y187 P loc C Gab1 PH PRS1_PRS2 T312 O P S381 O P Y447 O P S454 1O 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 1STkinase 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 1O 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 1STkinase 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 1O 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 1STkinase 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 1O 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 1 ⬆STkinase T185 O P Y187 O P loc C Gab1 PH PRS1_PRS2 1 ⬆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 1 ⬆STkinase T185 O P Y187 O P loc C Gab1 PH PRS1_PRS2 T312 O P 1 ⬆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 1 ⬆STkinase T185 O P Y187 O P loc C Gab1 PH PRS1_PRS2 T312 O P S381 O P Y447 O P 1 ⬆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 1 ⬆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 1 ⬆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 1 ⬆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 1 ⬆S581 S597 O P Y619 O P Y657 O P loc C

ERK2(STkinase!1).Gab1(S597!1) -> ERK2(STkinase) + Gab1(S597)

ERK2 CD 1 ⬆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 1 ⬆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 1 ⬇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 1 ⬇C3P two F loc M

Gab1(PH!1).PIP3(C3P!1) -> Gab1(PH) + PIP3(C3P)

Gab1 1 ⬆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 1 ⬆C3P two F T loc M
############# PI3K interactions ##############PI3K binds membrane localized Gab1-Grb2-Shc and Gab1-Grb2 at Y447,Y472, and Y619Y447

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 3 ⬇G_p85_nSH2_cSH2 p110_RBD loc C Gab1 PH 1PRS1_PRS2 T312 O S381 O Y447 3 ⬇P S454 O Y472 O P T476 O S581 O S597 O Y619 O P Y657 O P loc C Grb2 SH2r 2SH2s 1cSH3 nSH3 loc C p52Shc1 PTB Y317 2O 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 2 ⬇G_p85_nSH2_cSH2 p110_RBD loc C Gab1 PH 1PRS1_PRS2 T312 O S381 O Y447 2 ⬇P S454 O Y472 O P T476 O S581 O S597 O Y619 O P Y657 O P loc C Grb2 SH2r SH2s 1cSH3 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 3 ⬇G_p85_nSH2_cSH2 p110_RBD loc C Gab1 PH 1PRS1_PRS2 T312 O S381 O Y447 O P S454 O Y472 3 ⬇P T476 O S581 O S597 O Y619 O P Y657 O P loc C Grb2 SH2r 2SH2s 1cSH3 nSH3 loc C p52Shc1 PTB Y317 2O 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 2 ⬇G_p85_nSH2_cSH2 p110_RBD loc C Gab1 PH 1PRS1_PRS2 T312 O S381 O Y447 O P S454 O Y472 2 ⬇P T476 O S581 O S597 O Y619 O P Y657 O P loc C Grb2 SH2r SH2s 1cSH3 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 3 ⬇G_p85_nSH2_cSH2 p110_RBD loc C Gab1 PH 1PRS1_PRS2 T312 O S381 O Y447 O P S454 O Y472 O P T476 O S581 O S597 O Y619 3 ⬇P Y657 O P loc C Grb2 SH2r 2SH2s 1cSH3 nSH3 loc C p52Shc1 PTB Y317 2O 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 2 ⬇G_p85_nSH2_cSH2 p110_RBD loc C Gab1 PH 1PRS1_PRS2 T312 O S381 O Y447 O P S454 O Y472 O P T476 O S581 O S597 O Y619 2 ⬇P Y657 O P loc C Grb2 SH2r SH2s 1cSH3 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 2 ⬇G_p85_nSH2_cSH2 p110_RBD loc C Gab1 1PH PRS1_PRS2 T312 O S381 O Y447 2 ⬇P S454 O Y472 O P T476 O S581 O S597 O Y619 O P Y657 O P loc C PIP3 1C3P 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 2 ⬇G_p85_nSH2_cSH2 p110_RBD loc C Gab1 1PH PRS1_PRS2 T312 O S381 O Y447 O P S454 O Y472 2 ⬇P T476 O S581 O S597 O Y619 O P Y657 O P loc C PIP3 1C3P 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 2 ⬇G_p85_nSH2_cSH2 p110_RBD loc C Gab1 1PH PRS1_PRS2 T312 O S381 O Y447 O P S454 O Y472 O P T476 O S581 O S597 O Y619 2 ⬇P Y657 O P loc C PIP3 1C3P 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 1 ⬆G_p85_nSH2_cSH2 p110_RBD loc C Gab1 PH PRS1_PRS2 T312 O P S381 O P 1 ⬆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 1 ⬆G_p85_nSH2_cSH2 p110_RBD loc C Gab1 PH PRS1_PRS2 T312 O P S381 O P Y447 O P S454 O P 1 ⬆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 1 ⬆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 1 ⬆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 3G_p85_nSH2_cSH2 4 ⬇p110_RBD loc C Gab1 PH 1PRS1_PRS2 T312 O P S381 O P Y447 3P 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 2SH2s 1cSH3 nSH3 loc C p52Shc1 PTB Y317 2P loc C KRas 4 ⬇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 2G_p85_nSH2_cSH2 4 ⬇p110_RBD loc C Gab1 PH 1PRS1_PRS2 T312 O P S381 O P Y447 2P 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 1cSH3 nSH3 loc C KRas 4 ⬇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 3G_p85_nSH2_cSH2 4 ⬇p110_RBD loc C Gab1 PH 1PRS1_PRS2 T312 O P S381 O P Y447 O P S454 O P Y472 3P T476 O P S581 O P S597 O P Y619 O P Y657 O P loc C Grb2 SH2r 2SH2s 1cSH3 nSH3 loc C p52Shc1 PTB Y317 2P loc C KRas 4 ⬇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 2G_p85_nSH2_cSH2 4 ⬇p110_RBD loc C Gab1 PH 1PRS1_PRS2 T312 O P S381 O P Y447 O P S454 O P Y472 2P T476 O P S581 O P S597 O P Y619 O P Y657 O P loc C Grb2 SH2r SH2s 1cSH3 nSH3 loc C KRas 4 ⬇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 3G_p85_nSH2_cSH2 4 ⬇p110_RBD loc C Gab1 PH 1PRS1_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 3P Y657 O P loc C Grb2 SH2r 2SH2s 1cSH3 nSH3 loc C p52Shc1 PTB Y317 2P loc C KRas 4 ⬇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 2G_p85_nSH2_cSH2 4 ⬇p110_RBD loc C Gab1 PH 1PRS1_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 2P Y657 O P loc C Grb2 SH2r SH2s 1cSH3 nSH3 loc C KRas 4 ⬇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 1 ⬆p110_RBD loc C KRas 1 ⬆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 1 ⬆⬇R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc C ErbB3 I_III II Y1054 1 ⬆⬇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 1 ⬆⬇R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc C ErbB3 I_III II Y1054 O P Y1197 1 ⬆⬇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 1 ⬆⬇R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc C ErbB3 I_III II Y1054 O P Y1197 O P Y1222 1 ⬆⬇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 1 ⬆⬇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 1 ⬆⬇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 1 ⬆⬇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 1 ⬆⬇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 1 ⬆⬇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 1 ⬆⬇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 1 ⬆⬇R_p85_nSH2_cSH2 G_p85_nSH2_cSH2 p110_RBD loc C ErbB4 I_III II Y1056 1 ⬆⬇P Y1188 O P Y1242 O P loc M En
############# PIP3 interactions ##############creation of PIP3 by active PI3K-Gab1~recWith PI3K bound to Rascreation of PIP3 by PI3k-Gab1-PIP3creation of PIP3 by PI3K-ErbB3PIP3 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 1 ⬆⬇PH STkinase T308 O P S473 O P loc C PIP3 1 ⬆⬇C3P two F loc M
PDK1 binding to PIP3

PDK1(PH) + PIP3(C3P,two~F) <-> PDK1(PH!1).PIP3(C3P!1,two~F)

PDK1 1 ⬆⬇PH STkinase loc C PIP3 1 ⬆⬇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 1 ⬇STkinase loc C Akt1 PH STkinase T308 1 ⬇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 1STkinase loc C Akt1 PH STkinase T308 1O 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 1 ⬆STkinase loc C Akt1 PH STkinase 1 ⬆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 S259This 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 1 ⬇STkinase T308 P S473 P loc C Raf1 RBD STkinase S29 O P S43 O P S259 1 ⬇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 1STkinase T308 P S473 P loc C Raf1 RBD STkinase S29 O P S43 O P S259 1O 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 1 ⬆STkinase T308 O P S473 O P loc C Raf1 RBD STkinase S29 O P S43 O P 1 ⬆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 1 ⬆⬇nSH2 GAP EGFR I_III II T669 O P Y992 1 ⬆⬇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 1 ⬇GAP KRas 1 ⬇GTPase g GTP loc M

p120RasGAP(GAP!1).KRas(GTPase!1,g~GTP) -> p120RasGAP(GAP!1).KRas(GTPase!1,g~GDP)

p120RasGAP nSH2 1GAP KRas 1GTPase 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 1 ⬆GAP KRas 1 ⬆GTPase g GDP GTP loc M