Molecules

Residue numbers, where applicable, are given for rat proteins.The ligand is DNP-BSA and is taken to have two virtual haptens.Each hapten has two possible states, buried (b) or exposed (e).

Lig(hap~b~e,hap~b~e)

Lig hap b e hap b e
The receptor is a complex of FceRI and an IgE antibody.The "fab" components represent the two fab arms of hapten-specific IgE.b_Y218 and b_Y224 are tyrosines in the ITAM of the beta subunit.b_Y224 is non-canonical, located between the two canonical tyrosines of the ITAM.Y65 and Y76 are tyrosines in the ITAM of the gamma subunit and are lumped as a single site.Only one (of the two) gamma chains is considered, as a simplification.

Rec(fab,fab,b_Y218~0~P,b_Y224~0~P,g_Y65_Y76~0~P)

Rec fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P
Lyn is an SFK with a unique domain (U), an SH2 domain, and an SH3 domain.Y397 is located in the kinase activation loop, and Y508 is the inhibitory C-terminal tyrosine.

Lyn(U,SH3,SH2,Y397~0~P,Y508~0~P)

Lyn U SH3 SH2 Y397 0 P Y508 0 P
Fyn is an SFK with a unique domain (U), an SH2 domain, and an SH3 domain.Y420 is located in the kinase activation loop, and Y531 is the inhibitory C-terminal tyrosine.

Fyn(U,SH3,SH2,PTK,Y420~0~P,Y531~0~P)

Fyn U SH3 SH2 PTK Y420 0 P Y531 0 P
Syk is a kinase with tandem SH2 domains, which are lumped as a single site.Y346 is located in Interdomain B.Y519 and Y520 are located in the activation loop of the kinase domain. These tyrosines are lumped as a single site.

Syk(tSH2,Y346~0~P,PTK,Y519_Y520~0~P)

Syk tSH2 Y346 0 P PTK Y519_Y520 0 P
Pag1 is an adaptor protein with two proline-rich sequences (PRS1 and PRS2) and multiple phosphosites.Y165 and Y183 are lumped as a single site, as are Y386 and Y409.PRS1 represents the PRIP motif starting at P136.PRS2 represents the PPVP motif starting at P255.

Pag1(PRS1,Y165_Y183~0~P,PRS2,Y317~0~P,Y386_Y409~0~P)

Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 0 P Y386_Y409 0 P
Csk is a kinase with an SH2 domain.

Csk(SH2)

Csk SH2
Lat is an adaptor protein with multiple tyrosine residues that undergo phosphorylation, of which we focus on Y136 and Y175

Lat(Y136~0~P,Y175~0~P)

Lat Y136 0 P Y175 0 P
Phospholipase C gamma 1 (Plcg1)

Plcg1(SH2,SH3,PLC,Y783~0~P)

Plcg1 SH2 SH3 PLC Y783 0 P
Grb2 is an adaptor protein with an SH2 domain and two SH3 domains, of which we consider the C-terminal domain.

Grb2(SH2,cSH3)

Grb2 SH2 cSH3
Gab2 is an adaptor protein

Gab2(PRS,Y441~0~P)

Gab2 PRS Y441 0 P
Grap2 is an adaptor protein

Grap2(SH2,SH3)

Grap2 SH2 SH3
Lcp2 is an adaptor protein

Lcp2(RxxK,PRS)

Lcp2 RxxK PRS
PI 3-kinase is a heterodimeric lipid kinase that can phosphorylate the 3 position of an inositol ring.Its p85 subunit contains an SH2 domain.

Pi3k(p85_SH2,PI3Kc)

Pi3k p85_SH2 PI3Kc
Btk is a Tec family kinase

Btk(PH,PTK)

Btk PH PTK
Inpp5d is an inositol phosphatase. It is also known as Ship1.It contains an SH2 domain, a C2 domain that can bind lipid species, and an inositol polyphosphate phosphatase catalytic domain (IPP)

Inpp5d(SH2,IPP,C2)

Inpp5d SH2 IPP C2
Phosphatidylinositol 3,4-bisphosphate, or PtdIns(3,4)P2, is a phospholipid.The "bind" component is a virtual site for protein interactions.

PI34P2(bind)

PI34P2 bind
Phosphatidylinositol 4,5-bisphosphate, or PtdIns(4,5)P2, is a phospholipid.The "bind" component is a virtual site for protein interactions.

PI45P2(bind)

PI45P2 bind
Phosphatidylinositol 3,4,5-trisphosphate, or PtdIns(3,4,5)P3, is a phospholipid.The "bind" component is a virtual site for protein interactions.

PI345P3(bind)

PI345P3 bind
Inositol 1,4,5-trisphosphate

IP3()

IP3
Diacyl glycerol

DAG()

DAG
Sink

Sink()

Sink

PI4P()

PI4P

Species

Lig(hap~b,hap~b)

Lig hap b hap b

Rec(fab,fab,b_Y218~0,b_Y224~0,g_Y65_Y76~0)

Rec fab fab b_Y218 0 b_Y224 0 g_Y65_Y76 0

Lyn(U,SH2,SH3,Y397~0,Y508~0)

Lyn U SH2 SH3 Y397 0 Y508 0

Fyn(U,SH2,SH3,Y420~0,PTK,Y531~0)

Fyn U SH2 SH3 Y420 0 PTK Y531 0

Syk(tSH2,Y346~0,PTK,Y519_Y520~0)

Syk tSH2 Y346 0 PTK Y519_Y520 0

Pag1(PRS1,PRS2,Y317~0,Y165_Y183~0,Y386_Y409~0)

Pag1 PRS1 PRS2 Y317 0 Y165_Y183 0 Y386_Y409 0

Csk(SH2)

Csk SH2

Lat(Y136~0,Y175~0)

Lat Y136 0 Y175 0

Plcg1(SH2,SH3,PLC,Y783~0)

Plcg1 SH2 SH3 PLC Y783 0

Grb2(SH2,cSH3)

Grb2 SH2 cSH3

Gab2(PRS,Y441~0)

Gab2 PRS Y441 0

PI45P2(bind)

PI45P2 bind

Pi3k(PI3Kc,p85_SH2)

Pi3k PI3Kc p85_SH2

Btk(PH,PTK)

Btk PH PTK

Inpp5d(SH2,C2,IPP)

Inpp5d SH2 C2 IPP

Grap2(SH2,SH3)

Grap2 SH2 SH3

Lcp2(RxxK,PRS)

Lcp2 RxxK PRS

PI4P()

PI4P

Sink()

Sink

Observables

Lat(Y136~P!?)

Lat Y136 P Y175 0 P

Lat(Y175~P!?)

Lat Y136 0 P Y175 P

Rec(b_Y218~P!?)

Rec fab fab b_Y218 P b_Y224 0 P g_Y65_Y76 0 P

Rec(b_Y224~P!?)

Rec fab fab b_Y218 0 P b_Y224 P g_Y65_Y76 0 P

Rec(g_Y65_Y76~P!?)

Rec fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 P

Syk(Y346~P!?)

Syk tSH2 Y346 P PTK Y519_Y520 0 P

Gab2(Y441~P!?)

Gab2 PRS Y441 P

Lat(Y175~P!1).Grb2(SH2!1,cSH3!2).Gab2(PRS!2,Y441~P!3).Pi3k(p85_SH2!3)

Lat Y136 0 P Y175 1P Grb2 1SH2 2cSH3 Gab2 2PRS Y441 3P Pi3k 3p85_SH2 PI3Kc

PI345P3(bind!?)

PI345P3 bind

Plcg1(Y783~P!?)

Plcg1 SH2 SH3 PLC Y783 P

Lyn(U!+)

Lyn U SH3 SH2 Y397 0 P Y508 0 P

Lyn(SH2!+)

Lyn U SH3 SH2 Y397 0 P Y508 0 P

Inpp5d(SH2!+)

Inpp5d SH2 IPP C2

Plcg1(PLC!1).PI45P2(bind!1)

Plcg1 SH2 SH3 1PLC Y783 0 P PI45P2 1bind

Lat(Y136~P!1).Plcg1(SH2!1)

Lat Y136 1P Y175 0 P Plcg1 1SH2 SH3 PLC Y783 0 P

IP3()

IP3

PI34P2(bind!?)

PI34P2 bind

PI45P2(bind!?)

PI45P2 bind

Pag1(Y165_Y183~P!?)

Pag1 PRS1 Y165_Y183 P PRS2 Y317 0 P Y386_Y409 0 P

Pag1(Y386_Y409~P!?)

Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 0 P Y386_Y409 P

Lyn(SH2!1,Y508~P!1)

Lyn U SH3 1SH2 Y397 0 P Y508 1P

Fyn(SH2!1,Y531~P!1)

Fyn U SH3 1SH2 PTK Y420 0 P Y531 1P

Lyn(Y508~P!?)

Lyn U SH3 SH2 Y397 0 P Y508 P

Fyn(Y531~P!?)

Fyn U SH3 SH2 PTK Y420 0 P Y531 P

Btk(PH!+)

Btk PH PTK
Free ligand

Lig(hap,hap)

Lig hap hap
Crosslinked receptor dimer

Lig(hap~e!1,hap~e!2).Rec(fab!1).Rec(fab!2)

Lig hap 1e hap 2e Rec 1fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P Rec 2fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P
Ligand with both haptens buried

Lig(hap~b!?,hap~b!?)

Lig hap b hap b
Ligand with one hapten exposed

Lig(hap~b!?,hap~e!?)

Lig hap b hap e
Ligand with both haptens exposed

Lig(hap~e!?,hap~e!?)

Lig hap e hap e
Total ligand

Lig(hap!?,hap!?)

Lig hap hap

Syk(Y519_Y520~P)

Syk tSH2 Y346 0 P PTK Y519_Y520 P

Reaction Rules

Haptens are transiently exposed.

Lig(hap~b) <-> Lig(hap~e)

Lig hap b e take all branches, once each, in any order⬇⬇ hap b e
Binding from solution when a hapten is exposed. Does not depend on state of second hapten.

Lig(hap~e,hap~e) + Rec(fab) -> Lig(hap~e,hap~e!1).Rec(fab!1)

Lig hap e hap 1 ⬇e Rec 1 ⬇fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P

Lig(hap~b,hap~e) + Rec(fab) -> Lig(hap~b,hap~e!1).Rec(fab!1)

Lig hap b hap 1 ⬇e Rec 1 ⬇fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P
Receptor crosslinking when both haptens are exposed.

Lig(hap~e,hap~e!1).Rec(fab!1) + Rec(fab) -> Lig(hap~e!2,hap~e!1).Rec(fab!1).Rec(fab!2)

Lig hap 2 ⬇e hap 1e Rec 1fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P Rec 2 ⬇fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P
Dissociation of hapten from receptor site

Lig(hap~e!1).Rec(fab!1) -> Lig(hap~e) + Rec(fab)

Lig hap 1 ⬆e hap b e Rec 1 ⬆fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P
Lyn unique domain binds receptor

Rec(b_Y218~0) + Lyn(U,SH3,SH2) -> Rec(b_Y218~0!1).Lyn(U!1,SH3,SH2)

Rec fab fab b_Y218 1 ⬇0 b_Y224 0 P g_Y65_Y76 0 P Lyn 1 ⬇U SH3 SH2 Y397 0 P Y508 0 P
Lyn unique domain dissociates from receptor

Rec(b_Y218~0!1).Lyn(U!1) -> Rec(b_Y218~0) + Lyn(U)

Rec fab fab b_Y218 1 ⬆0 b_Y224 0 P g_Y65_Y76 0 P Lyn 1 ⬆U SH3 SH2 Y397 0 P Y508 0 P
Lyn SH2 domain binds receptor

Rec(b_Y218~P) + Lyn(U,SH3,SH2) -> Rec(b_Y218~P!1).Lyn(U,SH3,SH2!1)

Rec fab fab b_Y218 1 ⬇P b_Y224 0 P g_Y65_Y76 0 P Lyn U SH3 1 ⬇SH2 Y397 0 P Y508 0 P
Lyn SH2 domain dissociates from receptor

Rec(b_Y218~P!1).Lyn(SH2!1) -> Rec(b_Y218~P) + Lyn(SH2)

Rec fab fab b_Y218 1 ⬆P b_Y224 0 P g_Y65_Y76 0 P Lyn U SH3 1 ⬆SH2 Y397 0 P Y508 0 P
Lyn SH2 domain binds Lyn pY508, forming an intramolecular bond

Lyn(U,SH3,SH2,Y508~P) -> Lyn(U,SH3,SH2!1,Y508~P!1)

Lyn U SH3 1 ⬇SH2 Y397 0 P Y508 1 ⬇P
Lyn SH2 dissociates from Lyn pY508

Lyn(SH2!1,Y508~P!1) -> Lyn(SH2,Y508~P)

Lyn U SH3 1 ⬆SH2 Y397 0 P Y508 1 ⬆P
# Lyn phosphorylates Y218 in the beta subunit of the receptor.Lyn bound by its unqiue domain

Lyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y218~0) -> Lyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y218~P)

Lyn 1U SH3 SH2 Y397 0 P Y508 0 P Rec 2fab fab b_Y218 10 b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P take all branches, once each, in any order⬇⬇ b_Y224 0 P g_Y65_Y76 0 P
Lyn bound by its SH2 domain

Lyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y218~0) -> Lyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y218~P)

Lyn U SH3 1SH2 Y397 0 P Y508 0 P Rec 2fab fab b_Y218 1P b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P take all branches, once each, in any order⬇⬇ b_Y224 0 P g_Y65_Y76 0 P
# Lyn phosphorylates Y224 in the beta subunit of the receptor.Lyn bound by its unqiue domain

Lyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y224~0) -> Lyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y224~P)

Lyn 1U SH3 SH2 Y397 0 P Y508 0 P Rec 2fab fab b_Y218 10 b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P take all branches, once each, in any order⬇⬇ g_Y65_Y76 0 P
Lyn bound by its SH2 domain

Lyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y224~0) -> Lyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y224~P)

Lyn U SH3 1SH2 Y397 0 P Y508 0 P Rec 2fab fab b_Y218 1P b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P take all branches, once each, in any order⬇⬇ g_Y65_Y76 0 P
# Lyn phosphorylates Y65 and Y76 in the gamma subunit of the receptor.Lyn bound by its unqiue domain

Lyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~0) -> Lyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P)

Lyn 1U SH3 SH2 Y397 0 P Y508 0 P Rec 2fab fab b_Y218 10 b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P take all branches, once each, in any order⬇⬇
Lyn bound by its SH2 domain

Lyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~0) -> Lyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P)

Lyn U SH3 1SH2 Y397 0 P Y508 0 P Rec 2fab fab b_Y218 1P b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P take all branches, once each, in any order⬇⬇
Syk binds the dually phosphorylated gamma subunit of the receptor

Syk(tSH2) + Rec(g_Y65_Y76~P) <-> Syk(tSH2!1).Rec(g_Y65_Y76~P!1)

Syk 1 ⬆⬇tSH2 Y346 0 P PTK Y519_Y520 0 P Rec fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 1 ⬆⬇P
# Lyn phosphorylates SykLyn bound by its unique domain

Lyn(U!1).Rec(fab!2,b_Y218~0!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y346~0) -> Lyn(U!1).Rec(fab!2,b_Y218~0!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y346~P)

Lyn 1U SH3 SH2 Y397 0 P Y508 0 P Rec 2fab fab b_Y218 10 b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 4P Syk 4tSH2 Y346 0 P take all branches, once each, in any order⬇⬇ PTK Y519_Y520 0 P
Lyn bound by its SH2 domain

Lyn(SH2!1).Rec(fab!2,b_Y218~P!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y346~0) -> Lyn(SH2!1).Rec(fab!2,b_Y218~P!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y346~P)

Lyn U SH3 1SH2 Y397 0 P Y508 0 P Rec 2fab fab b_Y218 1P b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 4P Syk 4tSH2 Y346 0 P take all branches, once each, in any order⬇⬇ PTK Y519_Y520 0 P
# Syk trans-phosphorylates the activation loop tyrosine of another Syk moleculeSyk unphosphorlyated on activation loop

Syk(tSH2!1,Y519_Y520~0).Rec(fab!2,g_Y65_Y76~P!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y519_Y520~0) -> Syk(tSH2!1,Y519_Y520~0).Rec(fab!2,g_Y65_Y76~P!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y519_Y520~P)

Syk 1tSH2 Y346 0 P PTK Y519_Y520 0 Rec 2fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 1P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 4P Syk 4tSH2 Y346 0 P PTK Y519_Y520 0 P take all branches, once each, in any order⬇⬇
Syk phosphorylated on activation loop

Syk(tSH2!1,Y519_Y520~P).Rec(fab!2,g_Y65_Y76~P!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y519_Y520~0) -> Syk(tSH2!1,Y519_Y520~P).Rec(fab!2,g_Y65_Y76~P!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y519_Y520~P)

Syk 1tSH2 Y346 0 P PTK Y519_Y520 P Rec 2fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 1P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 4P Syk 4tSH2 Y346 0 P PTK Y519_Y520 0 P take all branches, once each, in any order⬇⬇
# SH3 domain of Lyn binds PRS2 in Pag1Association when Lyn is free

Lyn(U,SH3,SH2) + Pag1(PRS2,Y386_Y409) -> Lyn(U,SH3!1,SH2).Pag1(PRS2!1,Y386_Y409)

Lyn U 1 ⬇SH3 SH2 Y397 0 P Y508 0 P Pag1 PRS1 Y165_Y183 0 P 1 ⬇PRS2 Y317 0 P Y386_Y409
Association when Lyn is tethered to Pag1 by an SH2 domain-pY interactionLyn, already tethered in Pag1 by SH2, binds Pag1 via SH3 domain

Lyn(U,SH3,SH2!2).Pag1(PRS2,Y386_Y409~P!2) -> Lyn(U,SH3!1,SH2!2).Pag1(PRS2!1,Y386_Y409~P!2)

Lyn U 1 ⬇SH3 2SH2 Y397 0 P Y508 0 P Pag1 PRS1 Y165_Y183 0 P 1 ⬇PRS2 Y317 0 P Y386_Y409 2P
Dissociation of Lyn SH3

Lyn(SH3!1,SH2).Pag1(PRS2!1,Y386_Y409) -> Lyn(SH3,SH2) + Pag1(PRS2,Y386_Y409)

Lyn U 1 ⬆SH3 SH2 Y397 0 P Y508 0 P Pag1 PRS1 Y165_Y183 0 P 1 ⬆PRS2 Y317 0 P Y386_Y409
SH2 domain of Lyn binds a pY docking site in Pag1Association when Lyn is free

Lyn(U,SH3,SH2) + Pag1(PRS2,Y386_Y409~P) -> Lyn(U,SH3,SH2!2).Pag1(PRS2,Y386_Y409~P!2)

Lyn U SH3 2 ⬇SH2 Y397 0 P Y508 0 P Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 0 P Y386_Y409 2 ⬇P
Association when Lyn is tethered to Pag1 via an SH3 domain-PRS interaction

Lyn(U,SH3!1,SH2).Pag1(PRS2!1,Y386_Y409~P) -> Lyn(U,SH3!1,SH2!2).Pag1(PRS2!1,Y386_Y409~P!2)

Lyn U 1SH3 2 ⬇SH2 Y397 0 P Y508 0 P Pag1 PRS1 Y165_Y183 0 P 1PRS2 Y317 0 P Y386_Y409 2 ⬇P
Dissociation of Lyn from Pag1, breaking two-point attachmentBecause association of the Lyn SH3 domain with Pag1 PRS2 is rapid (relative to the lifetime of a pY-SH2 bond) when Lyn is tethered by its SH2 domain,we omit dissociation of the SH2 domain alone, as a simplification.

Lyn(SH3!1,SH2!2).Pag1(PRS2!1,Y386_Y409~P!2) -> Lyn(SH3,SH2) + Pag1(PRS2,Y386_Y409~P)

Lyn U 1 ⬆SH3 2 ⬆SH2 Y397 0 P Y508 0 P Pag1 PRS1 Y165_Y183 0 P 1 ⬆PRS2 Y317 0 P Y386_Y409 2 ⬆P
Lyn phosphorylates Y386 and Y409 in Pag1

Lyn(SH3!1,Y508).Pag1(PRS2!1,Y386_Y409~0) -> Lyn(SH3!1,Y508).Pag1(PRS2!1,Y386_Y409~P)

Lyn U 1SH3 SH2 Y397 0 P Y508 Pag1 PRS1 Y165_Y183 0 P 1PRS2 Y317 0 P Y386_Y409 0 P take all branches, once each, in any order⬇⬇
Lyn phosphorylates Y165 and Y183 in Pag1

Lyn(SH3,SH2!1,Y508).Pag1(Y165_Y183~0,Y386_Y409~P!1) -> Lyn(SH3,SH2!1,Y508).Pag1(Y165_Y183~P,Y386_Y409~P!1)

Lyn U SH3 1SH2 Y397 0 P Y508 Pag1 PRS1 Y165_Y183 0 P take all branches, once each, in any order⬇⬇ PRS2 Y317 0 P Y386_Y409 1P

Lyn(SH3!2,SH2!1,Y508).Pag1(PRS2!2,Y165_Y183~0,Y386_Y409~P!1) -> Lyn(SH3!2,SH2!1,Y508).Pag1(PRS2!2,Y165_Y183~P,Y386_Y409~P!1)

Lyn U 2SH3 1SH2 Y397 0 P Y508 Pag1 PRS1 Y165_Y183 0 P take all branches, once each, in any order⬇⬇ 2PRS2 Y317 0 P Y386_Y409 1P

Lyn(SH3!1,SH2,Y508).Pag1(PRS2!1,Y165_Y183~0) -> Lyn(SH3!1,SH2,Y508).Pag1(PRS2!1,Y165_Y183~P)

Lyn U 1SH3 SH2 Y397 0 P Y508 Pag1 PRS1 Y165_Y183 0 P take all branches, once each, in any order⬇⬇ 1PRS2 Y317 0 P Y386_Y409 0 P

Lyn(SH2!1,Y508).Pag1(Y317~0,Y386_Y409~P!1) -> Lyn(SH2!1,Y508).Pag1(Y317~P,Y386_Y409~P!1)

Lyn U SH3 1SH2 Y397 0 P Y508 Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 0 P take all branches, once each, in any order⬇⬇ Y386_Y409 1P
Lyn phosphorylates Y317 in Pag1

Lyn(SH3,SH2!1,Y508).Pag1(Y317~0,Y386_Y409~P!1) -> Lyn(SH3,SH2!1,Y508).Pag1(Y317~P,Y386_Y409~P!1)

Lyn U SH3 1SH2 Y397 0 P Y508 Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 0 P take all branches, once each, in any order⬇⬇ Y386_Y409 1P

Lyn(SH3!2,SH2!1,Y508).Pag1(PRS2!2,Y317~0,Y386_Y409~P!1) -> Lyn(SH3!2,SH2!1,Y508).Pag1(PRS2!2,Y317~P,Y386_Y409~P!1)

Lyn U 2SH3 1SH2 Y397 0 P Y508 Pag1 PRS1 Y165_Y183 0 P 2PRS2 Y317 0 P take all branches, once each, in any order⬇⬇ Y386_Y409 1P

Lyn(SH3!1,SH2,Y508).Pag1(PRS2!1,Y317~0) -> Lyn(SH3!1,SH2,Y508).Pag1(PRS2!1,Y317~P)

Lyn U 1SH3 SH2 Y397 0 P Y508 Pag1 PRS1 Y165_Y183 0 P 1PRS2 Y317 0 P take all branches, once each, in any order⬇⬇ Y386_Y409 0 P
SH2 domain of Csk binds pY317 docking site in Pag1

Csk(SH2) + Pag1(Y317~P) <-> Csk(SH2!3).Pag1(Y317~P!3)

Csk 3 ⬆⬇SH2 Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 3 ⬆⬇P Y386_Y409 0 P
Csk cis phosphorylates Y508 in Lyn

Lyn(SH3,SH2!1,Y508~0).Pag1(Y386_Y409~P!1,Y317~P!2).Csk(SH2!2) -> Lyn(SH3,SH2!1,Y508~P).Pag1(Y386_Y409~P!1,Y317~P!2).Csk(SH2!2)

Lyn U SH3 1SH2 Y397 0 P Y508 0 P take all branches, once each, in any order⬇⬇ Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 2P Y386_Y409 1P Csk 2SH2

Lyn(SH3!1,SH2,Y508~0).Pag1(PRS2!1,Y317~P!2).Csk(SH2!2) -> Lyn(SH3!1,SH2,Y508~P).Pag1(PRS2!1,Y317~P!2).Csk(SH2!2)

Lyn U 1SH3 SH2 Y397 0 P Y508 0 P take all branches, once each, in any order⬇⬇ Pag1 PRS1 Y165_Y183 0 P 1PRS2 Y317 2P Y386_Y409 0 P Csk 2SH2

Lyn(SH3!1,SH2!3,Y508~0).Pag1(PRS2!1,Y386_Y409~P!3,Y317~P!2).Csk(SH2!2) -> Lyn(SH3!1,SH2!3,Y508~P).Pag1(PRS2!1,Y386_Y409~P!3,Y317~P!2).Csk(SH2!2)

Lyn U 1SH3 3SH2 Y397 0 P Y508 0 P take all branches, once each, in any order⬇⬇ Pag1 PRS1 Y165_Y183 0 P 1PRS2 Y317 2P Y386_Y409 3P Csk 2SH2
Fyn unique domain binds receptor

Rec(b_Y218~0) + Fyn(U,SH3,SH2) -> Rec(b_Y218~0!1).Fyn(U!1,SH3,SH2)

Rec fab fab b_Y218 1 ⬇0 b_Y224 0 P g_Y65_Y76 0 P Fyn 1 ⬇U SH3 SH2 PTK Y420 0 P Y531 0 P
Fyn unique domain dissociates from receptor

Rec(b_Y218~0!1).Fyn(U!1) -> Rec(b_Y218~0) + Fyn(U)

Rec fab fab b_Y218 1 ⬆0 b_Y224 0 P g_Y65_Y76 0 P Fyn 1 ⬆U SH3 SH2 PTK Y420 0 P Y531 0 P
Fyn SH2 domain binds receptor

Rec(b_Y218~P) + Fyn(U,SH3,SH2) -> Rec(b_Y218~P!1).Fyn(U,SH3,SH2!1)

Rec fab fab b_Y218 1 ⬇P b_Y224 0 P g_Y65_Y76 0 P Fyn U SH3 1 ⬇SH2 PTK Y420 0 P Y531 0 P
Fyn SH2 domain dissociates from receptor

Rec(b_Y218~P!1).Fyn(SH2!1) -> Rec(b_Y218~P) + Fyn(SH2)

Rec fab fab b_Y218 1 ⬆P b_Y224 0 P g_Y65_Y76 0 P Fyn U SH3 1 ⬆SH2 PTK Y420 0 P Y531 0 P
Fyn SH2 domain binds Fyn pY531, forming an intramolecular bond

Fyn(U,SH3,SH2,Y531~P) -> Fyn(U,SH3,SH2!1,Y531~P!1)

Fyn U SH3 1 ⬇SH2 PTK Y420 0 P Y531 1 ⬇P
Fyn SH2 domain dissociates from pY531

Fyn(SH2!1,Y531~P!1) -> Fyn(SH2,Y531~P)

Fyn U SH3 1 ⬆SH2 PTK Y420 0 P Y531 1 ⬆P
Fyn phosphorylates Y218 in the beta subunit of the receptorFyn bound by its unique domain

Fyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y218~0) -> Fyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y218~P)

Fyn 1U SH3 SH2 PTK Y420 0 P Y531 0 P Rec 2fab fab b_Y218 10 b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P take all branches, once each, in any order⬇⬇ b_Y224 0 P g_Y65_Y76 0 P
Fyn bound by its SH2 domain

Fyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y218~0) -> Fyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y218~P)

Fyn U SH3 1SH2 PTK Y420 0 P Y531 0 P Rec 2fab fab b_Y218 1P b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P take all branches, once each, in any order⬇⬇ b_Y224 0 P g_Y65_Y76 0 P
Fyn phosphorylates Y224 in the beta subunit of the receptorFyn bound by its unique domain

Fyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y224~0) -> Fyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y224~P)

Fyn 1U SH3 SH2 PTK Y420 0 P Y531 0 P Rec 2fab fab b_Y218 10 b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P take all branches, once each, in any order⬇⬇ g_Y65_Y76 0 P
Fyn bound by its SH2 domain

Fyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y224~0) -> Fyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,b_Y224~P)

Fyn U SH3 1SH2 PTK Y420 0 P Y531 0 P Rec 2fab fab b_Y218 1P b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P take all branches, once each, in any order⬇⬇ g_Y65_Y76 0 P
Fyn phosphorylates Y65 and Y76 in the gamma subunit of the receptorFyn bound by its unique domain

Fyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~0) -> Fyn(U!1).Rec(b_Y218~0!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P)

Fyn 1U SH3 SH2 PTK Y420 0 P Y531 0 P Rec 2fab fab b_Y218 10 b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P take all branches, once each, in any order⬇⬇
Fyn bound by its SH2 domain

Fyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~0) -> Fyn(SH2!1).Rec(b_Y218~P!1,fab!2).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P)

Fyn U SH3 1SH2 PTK Y420 0 P Y531 0 P Rec 2fab fab b_Y218 1P b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P take all branches, once each, in any order⬇⬇
# Fyn phosphorylates SykFyn bound by its unique domain

Fyn(U!1).Rec(fab!2,b_Y218~0!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y346~0) -> Fyn(U!1).Rec(fab!2,b_Y218~0!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y346~P)

Fyn 1U SH3 SH2 PTK Y420 0 P Y531 0 P Rec 2fab fab b_Y218 10 b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 4P Syk 4tSH2 Y346 0 P take all branches, once each, in any order⬇⬇ PTK Y519_Y520 0 P
Fyn bound by its SH2 domain

Fyn(SH2!1).Rec(fab!2,b_Y218~P!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y346~0) -> Fyn(SH2!1).Rec(fab!2,b_Y218~P!1).Lig(hap~e!2,hap~e!3).Rec(fab!3,g_Y65_Y76~P!4).Syk(tSH2!4,Y346~P)

Fyn U SH3 1SH2 PTK Y420 0 P Y531 0 P Rec 2fab fab b_Y218 1P b_Y224 0 P g_Y65_Y76 0 P Lig hap 2e hap 3e Rec 3fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 4P Syk 4tSH2 Y346 0 P take all branches, once each, in any order⬇⬇ PTK Y519_Y520 0 P
# SH3 domain of Fyn binds PRS1 in Pag1Association when Fyn is free

Fyn(U,SH3,SH2) + Pag1(PRS1,Y165_Y183) -> Fyn(U,SH3!1,SH2).Pag1(PRS1!1,Y165_Y183)

Fyn U 1 ⬇SH3 SH2 PTK Y420 0 P Y531 0 P Pag1 1 ⬇PRS1 Y165_Y183 PRS2 Y317 0 P Y386_Y409 0 P
Association when Fyn is tethered to Pag1 via an SH2 domain-pY interaction

Fyn(U,SH3,SH2!2).Pag1(PRS1,Y165_Y183~P!2) -> Fyn(U,SH3!1,SH2!2).Pag1(PRS1!1,Y165_Y183~P!2)

Fyn U 1 ⬇SH3 2SH2 PTK Y420 0 P Y531 0 P Pag1 1 ⬇PRS1 Y165_Y183 2P PRS2 Y317 0 P Y386_Y409 0 P
Dissociation of Fyn SH3

Fyn(SH3!1,SH2).Pag1(PRS1!1,Y165_Y183) -> Fyn(SH3,SH2) + Pag1(PRS1,Y165_Y183)

Fyn U 1 ⬆SH3 SH2 PTK Y420 0 P Y531 0 P Pag1 1 ⬆PRS1 Y165_Y183 PRS2 Y317 0 P Y386_Y409 0 P
# SH2 domain of Fyn binds a pY in Pag1Association when Fyn is free

Fyn(U,SH3,SH2) + Pag1(PRS1,Y165_Y183~P) -> Fyn(U,SH3,SH2!2).Pag1(PRS1,Y165_Y183~P!2)

Fyn U SH3 2 ⬇SH2 PTK Y420 0 P Y531 0 P Pag1 PRS1 Y165_Y183 2 ⬇P PRS2 Y317 0 P Y386_Y409 0 P
Association when Fyn is tethered to Pag1 via SH3 domain-PRS interaction

Fyn(U,SH3!1,SH2).Pag1(PRS1!1,Y165_Y183~P) -> Fyn(U,SH3!1,SH2!2).Pag1(PRS1!1,Y165_Y183~P!2)

Fyn U 1SH3 2 ⬇SH2 PTK Y420 0 P Y531 0 P Pag1 1PRS1 Y165_Y183 2 ⬇P PRS2 Y317 0 P Y386_Y409 0 P
Dissociation of Fyn from Pag1, breaking two-point attachment

Fyn(SH3!1,SH2!2).Pag1(PRS1!1,Y165_Y183~P!2) -> Fyn(SH3,SH2) + Pag1(PRS1,Y165_Y183~P)

Fyn U 1 ⬆SH3 2 ⬆SH2 PTK Y420 0 P Y531 0 P Pag1 1 ⬆PRS1 Y165_Y183 2 ⬆P PRS2 Y317 0 P Y386_Y409 0 P
Fyn phosphorylates Y386 and Y409 in Pag1

Fyn(SH3,SH2!1,Y531).Pag1(Y386_Y409~0,Y165_Y183~P!1) -> Fyn(SH3,SH2!1,Y531).Pag1(Y386_Y409~P,Y165_Y183~P!1)

Fyn U SH3 1SH2 PTK Y420 0 P Y531 Pag1 PRS1 Y165_Y183 1P PRS2 Y317 0 P Y386_Y409 0 P take all branches, once each, in any order⬇⬇

Fyn(SH3!2,SH2!1,Y531).Pag1(PRS1!2,Y386_Y409~0,Y165_Y183~P!1) -> Fyn(SH3!2,SH2!1,Y531).Pag1(PRS1!2,Y386_Y409~P,Y165_Y183~P!1)

Fyn U 2SH3 1SH2 PTK Y420 0 P Y531 Pag1 2PRS1 Y165_Y183 1P PRS2 Y317 0 P Y386_Y409 0 P take all branches, once each, in any order⬇⬇

Fyn(SH3!1,SH2,Y531).Pag1(PRS1!1,Y386_Y409~0) -> Fyn(SH3!1,SH2,Y531).Pag1(PRS1!1,Y386_Y409~P)

Fyn U 1SH3 SH2 PTK Y420 0 P Y531 Pag1 1PRS1 Y165_Y183 0 P PRS2 Y317 0 P Y386_Y409 0 P take all branches, once each, in any order⬇⬇
Fyn phosphorylates Y317 in Pag1

Fyn(SH3,SH2!1,Y531).Pag1(Y317~0,Y165_Y183~P!1) -> Fyn(SH3,SH2!1,Y531).Pag1(Y317~P,Y165_Y183~P!1)

Fyn U SH3 1SH2 PTK Y420 0 P Y531 Pag1 PRS1 Y165_Y183 1P PRS2 Y317 0 P take all branches, once each, in any order⬇⬇ Y386_Y409 0 P

Fyn(SH3!2,SH2!1,Y531).Pag1(PRS1!2,Y317~0,Y165_Y183~P!1) -> Fyn(SH3!2,SH2!1,Y531).Pag1(PRS1!2,Y317~P,Y165_Y183~P!1)

Fyn U 2SH3 1SH2 PTK Y420 0 P Y531 Pag1 2PRS1 Y165_Y183 1P PRS2 Y317 0 P take all branches, once each, in any order⬇⬇ Y386_Y409 0 P

Fyn(SH3!1,SH2,Y531).Pag1(PRS1!1,Y317~0) -> Fyn(SH3!1,SH2,Y531).Pag1(PRS1!1,Y317~P)

Fyn U 1SH3 SH2 PTK Y420 0 P Y531 Pag1 1PRS1 Y165_Y183 0 P PRS2 Y317 0 P take all branches, once each, in any order⬇⬇ Y386_Y409 0 P
Csk cis phosphorylates Y531 in Fyn

Fyn(SH3,SH2!1,Y531~0).Pag1(Y165_Y183~P!1,Y317~P!2).Csk(SH2!2) -> Fyn(SH3,SH2!1,Y531~P).Pag1(Y165_Y183~P!1,Y317~P!2).Csk(SH2!2)

Fyn U SH3 1SH2 PTK Y420 0 P Y531 0 P take all branches, once each, in any order⬇⬇ Pag1 PRS1 Y165_Y183 1P PRS2 Y317 2P Y386_Y409 0 P Csk 2SH2

Fyn(SH3!1,SH2,Y531~0).Pag1(PRS1!1,Y317~P!2).Csk(SH2!2) -> Fyn(SH3!1,SH2,Y531~P).Pag1(PRS1!1,Y317~P!2).Csk(SH2!2)

Fyn U 1SH3 SH2 PTK Y420 0 P Y531 0 P take all branches, once each, in any order⬇⬇ Pag1 1PRS1 Y165_Y183 0 P PRS2 Y317 2P Y386_Y409 0 P Csk 2SH2

Fyn(SH3!1,SH2!3,Y531~0).Pag1(PRS1!1,Y165_Y183~P!3,Y317~P!2).Csk(SH2!2) -> Fyn(SH3!1,SH2!3,Y531~P).Pag1(PRS1!1,Y165_Y183~P!3,Y317~P!2).Csk(SH2!2)

Fyn U 1SH3 3SH2 PTK Y420 0 P Y531 0 P take all branches, once each, in any order⬇⬇ Pag1 1PRS1 Y165_Y183 3P PRS2 Y317 2P Y386_Y409 0 P Csk 2SH2
Syk phosphorylates Lat Y136

Syk(tSH2!+,PTK) + Lat(Y136~0) -> Syk(tSH2!+,PTK!1).Lat(Y136~0!1)

Syk tSH2 Y346 0 P 1 ⬇PTK Y519_Y520 0 P Lat Y136 1 ⬇0 Y175 0 P

Syk(PTK!1).Lat(Y136~0!1) -> Syk(PTK) + Lat(Y136~0)

Syk tSH2 Y346 0 P 1 ⬆PTK Y519_Y520 0 P Lat Y136 1 ⬆0 Y175 0 P

Syk(PTK!1,Y519_Y520~P).Lat(Y136~0!1) -> Syk(PTK,Y519_Y520~P) + Lat(Y136~P)

Syk tSH2 Y346 0 P 1 ⬆PTK Y519_Y520 P Lat Y136 1 ⬆0 P take all branches, once each, in any order⬇⬇ Y175 0 P

Syk(PTK!1,Y519_Y520~0).Lat(Y136~0!1) -> Syk(PTK,Y519_Y520~0) + Lat(Y136~P)

Syk tSH2 Y346 0 P 1 ⬆PTK Y519_Y520 0 Lat Y136 1 ⬆0 P take all branches, once each, in any order⬇⬇ Y175 0 P
Lat pY136 binds Plcg1

Lat(Y136~P) + Plcg1(SH2) <-> Lat(Y136~P!1).Plcg1(SH2!1)

Lat Y136 1 ⬆⬇P Y175 0 P Plcg1 1 ⬆⬇SH2 SH3 PLC Y783 0 P
Syk phosphorylates Lat Y175

Syk(tSH2!+,PTK) + Lat(Y175~0) -> Syk(tSH2!+,PTK!1).Lat(Y175~0!1)

Syk tSH2 Y346 0 P 1 ⬇PTK Y519_Y520 0 P Lat Y136 0 P Y175 1 ⬇0

Syk(PTK!1).Lat(Y175~0!1) -> Syk(PTK) + Lat(Y175~0)

Syk tSH2 Y346 0 P 1 ⬆PTK Y519_Y520 0 P Lat Y136 0 P Y175 1 ⬆0

Syk(PTK!1,Y519_Y520~P).Lat(Y175~0!1) -> Syk(PTK,Y519_Y520~P) + Lat(Y175~P)

Syk tSH2 Y346 0 P 1 ⬆PTK Y519_Y520 P Lat Y136 0 P Y175 1 ⬆0 P take all branches, once each, in any order⬇⬇

Syk(PTK!1,Y519_Y520~0).Lat(Y175~0!1) -> Syk(PTK,Y519_Y520~0) + Lat(Y175~P)

Syk tSH2 Y346 0 P 1 ⬆PTK Y519_Y520 0 Lat Y136 0 P Y175 1 ⬆0 P take all branches, once each, in any order⬇⬇
Lat pY175 binds Grb2

Lat(Y175~P) + Grb2(SH2) <-> Lat(Y175~P!1).Grb2(SH2!1)

Lat Y136 0 P Y175 1 ⬆⬇P Grb2 1 ⬆⬇SH2 cSH3
Lat pY175 binds Grap2

Lat(Y175~P) + Grap2(SH2) <-> Lat(Y175~P!1).Grap2(SH2!1)

Lat Y136 0 P Y175 1 ⬆⬇P Grap2 1 ⬆⬇SH2 SH3
Grap2 binds Lcp2

Grap2(SH3) + Lcp2(RxxK) <-> Grap2(SH3!1).Lcp2(RxxK!1)

Grap2 SH2 1 ⬆⬇SH3 Lcp2 1 ⬆⬇RxxK PRS
Grb2 binds Gab2

Grb2(cSH3) + Gab2(PRS) <-> Grb2(cSH3!1).Gab2(PRS!1)

Grb2 SH2 1 ⬆⬇cSH3 Gab2 1 ⬆⬇PRS Y441 0 P
Lcp2 binds Plcg1

Lcp2(PRS) + Plcg1(SH3) <-> Lcp2(PRS!1).Plcg1(SH3!1)

Lcp2 RxxK 1 ⬆⬇PRS Plcg1 SH2 1 ⬆⬇SH3 PLC Y783 0 P
Fyn phosphorylates Gab2

Fyn(U!+,SH2,PTK) + Lat(Y175~P!1).Grb2(SH2!1,cSH3!2).Gab2(PRS!2,Y441~0) -> Fyn(U!+,SH2,PTK!3).Lat(Y175~P!1).Grb2(SH2!1,cSH3!2).Gab2(PRS!2,Y441~0!3)

Fyn U SH3 SH2 3 ⬇PTK Y420 0 P Y531 0 P Lat Y136 0 P Y175 1P Grb2 1SH2 2cSH3 Gab2 2PRS Y441 3 ⬇0

Rec(b_Y218~P!4).Fyn(U,SH2!4,PTK) + Lat(Y175~P!1).Grb2(SH2!1,cSH3!2).Gab2(PRS!2,Y441~0) -> Rec(b_Y218~P!4).Fyn(U,SH2!4,PTK!3).Lat(Y175~P!1).Grb2(SH2!1,cSH3!2).Gab2(PRS!2,Y441~0!3)

Rec fab fab b_Y218 4P b_Y224 0 P g_Y65_Y76 0 P Fyn U SH3 4SH2 3 ⬇PTK Y420 0 P Y531 0 P Lat Y136 0 P Y175 1P Grb2 1SH2 2cSH3 Gab2 2PRS Y441 3 ⬇0

Fyn(PTK!1).Gab2(Y441~0!1) -> Fyn(PTK) + Gab2(Y441~0)

Fyn U SH3 SH2 1 ⬆PTK Y420 0 P Y531 0 P Gab2 PRS Y441 1 ⬆0

Fyn(PTK!1).Gab2(Y441~0!1) -> Fyn(PTK) + Gab2(Y441~P)

Fyn U SH3 SH2 1 ⬆PTK Y420 0 P Y531 0 P Gab2 PRS Y441 1 ⬆0 P take all branches, once each, in any order⬇⬇
Gab2 binds PI 3-kinase

Gab2(Y441~P) + Pi3k(p85_SH2) <-> Gab2(Y441~P!1).Pi3k(p85_SH2!1)

Gab2 PRS Y441 1 ⬆⬇P Pi3k 1 ⬆⬇p85_SH2 PI3Kc
PI 3-kinase generates PIP3

Lat(Y175~P!1).Grb2(SH2!1,cSH3!2).Gab2(PRS!2,Y441~P!3).Pi3k(p85_SH2!3,PI3Kc) + PI45P2(bind) -> Lat(Y175~P!1).Grb2(SH2!1,cSH3!2).Gab2(PRS!2,Y441~P!3).Pi3k(p85_SH2!3,PI3Kc!4).PI45P2(bind!4)

Lat Y136 0 P Y175 1P Grb2 1SH2 2cSH3 Gab2 2PRS Y441 3P Pi3k 3p85_SH2 4 ⬇PI3Kc PI45P2 4 ⬇bind

Pi3k(PI3Kc!1).PI45P2(bind!1) -> Pi3k(PI3Kc) + PI45P2(bind)

Pi3k p85_SH2 1 ⬆PI3Kc PI45P2 1 ⬆bind
Btk binds PIP3

Btk(PH) + PI345P3(bind) <-> Btk(PH!1).PI345P3(bind!1)

Btk 1 ⬆⬇PH PTK PI345P3 1 ⬆⬇bind
Btk phosphorylates Plcg1

Btk(PH!+,PTK) + Plcg1(SH2!+,Y783~0) -> Btk(PH!+,PTK!1).Plcg1(SH2!+,Y783~0!1)

Btk PH 1 ⬇PTK Plcg1 SH2 SH3 PLC Y783 1 ⬇0

Btk(PTK!1).Plcg1(Y783~0!1) -> Btk(PTK) + Plcg1(Y783~0)

Btk PH 1 ⬆PTK Plcg1 SH2 SH3 PLC Y783 1 ⬆0

Btk(PTK!1).Plcg1(Y783~0!1) -> Btk(PTK) + Plcg1(Y783~P)

Btk PH 1 ⬆PTK Plcg1 SH2 SH3 PLC Y783 1 ⬆0 P take all branches, once each, in any order⬇⬇
Inpp5d binds phosphorylated Y224 in the beta subunit of the receptor

Inpp5d(SH2,C2) + Rec(b_Y224~P) -> Inpp5d(SH2!1,C2).Rec(b_Y224~P!1)

Inpp5d 1 ⬇SH2 IPP C2 Rec fab fab b_Y218 0 P b_Y224 1 ⬇P g_Y65_Y76 0 P

Inpp5d(IPP,C2!+) + Rec(b_Y224~P) -> Inpp5d(IPP!1,C2!+).Rec(b_Y224~P!1)

Inpp5d SH2 1 ⬇IPP C2 Rec fab fab b_Y218 0 P b_Y224 1 ⬇P g_Y65_Y76 0 P

Inpp5d(SH2!1).Rec(b_Y224~P!1) -> Inpp5d(SH2) + Rec(b_Y224~P)

Inpp5d 1 ⬆SH2 IPP C2 Rec fab fab b_Y218 0 P b_Y224 1 ⬆P g_Y65_Y76 0 P

Inpp5d(SH2!+,IPP) + PI345P3(bind) <-> Inpp5d(SH2!+,IPP!1).PI345P3(bind!1)

Inpp5d SH2 1 ⬆⬇IPP C2 PI345P3 1 ⬆⬇bind
Other lipid reactionsNonspecific phosphorylation and dephosphorylation

Rec(b_Y218~0) -> Rec(b_Y218~P)

Rec fab fab b_Y218 0 P take all branches, once each, in any order⬇⬇ b_Y224 0 P g_Y65_Y76 0 P

Rec(b_Y218~P) -> Rec(b_Y218~0)

Rec fab fab b_Y218 0 P take one or more branches, once each, in any order⬆⬆ b_Y224 0 P g_Y65_Y76 0 P

Rec(b_Y224~0) -> Rec(b_Y224~P)

Rec fab fab b_Y218 0 P b_Y224 0 P take all branches, once each, in any order⬇⬇ g_Y65_Y76 0 P

Rec(b_Y224~P) -> Rec(b_Y224~0)

Rec fab fab b_Y218 0 P b_Y224 0 P take one or more branches, once each, in any order⬆⬆ g_Y65_Y76 0 P

Rec(g_Y65_Y76~0) -> Rec(g_Y65_Y76~P)

Rec fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P take all branches, once each, in any order⬇⬇

Rec(g_Y65_Y76~P) -> Rec(g_Y65_Y76~0)

Rec fab fab b_Y218 0 P b_Y224 0 P g_Y65_Y76 0 P take one or more branches, once each, in any order⬆⬆

Lyn(Y508~0) -> Lyn(Y508~P)

Lyn U SH3 SH2 Y397 0 P Y508 0 P take all branches, once each, in any order⬇⬇

Lyn(Y508~P) -> Lyn(Y508~0)

Lyn U SH3 SH2 Y397 0 P Y508 0 P take one or more branches, once each, in any order⬆⬆

Fyn(Y531~0) -> Fyn(Y531~P)

Fyn U SH3 SH2 PTK Y420 0 P Y531 0 P take all branches, once each, in any order⬇⬇

Fyn(Y531~P) -> Fyn(Y531~0)

Fyn U SH3 SH2 PTK Y420 0 P Y531 0 P take one or more branches, once each, in any order⬆⬆

Syk(Y346~0) -> Syk(Y346~P)

Syk tSH2 Y346 0 P take all branches, once each, in any order⬇⬇ PTK Y519_Y520 0 P

Syk(Y346~P) -> Syk(Y346~0)

Syk tSH2 Y346 0 P take one or more branches, once each, in any order⬆⬆ PTK Y519_Y520 0 P

Syk(Y519_Y520~0) -> Syk(Y519_Y520~P)

Syk tSH2 Y346 0 P PTK Y519_Y520 0 P take all branches, once each, in any order⬇⬇

Syk(Y519_Y520~P) -> Syk(Y519_Y520~0)

Syk tSH2 Y346 0 P PTK Y519_Y520 0 P take one or more branches, once each, in any order⬆⬆

Pag1(Y317~0) -> Pag1(Y317~P)

Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 0 P take all branches, once each, in any order⬇⬇ Y386_Y409 0 P

Pag1(Y317~P) -> Pag1(Y317~0)

Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 0 P take one or more branches, once each, in any order⬆⬆ Y386_Y409 0 P

Pag1(Y165_Y183~0) -> Pag1(Y165_Y183~P)

Pag1 PRS1 Y165_Y183 0 P take all branches, once each, in any order⬇⬇ PRS2 Y317 0 P Y386_Y409 0 P

Pag1(Y165_Y183~P) -> Pag1(Y165_Y183~0)

Pag1 PRS1 Y165_Y183 0 P take one or more branches, once each, in any order⬆⬆ PRS2 Y317 0 P Y386_Y409 0 P

Pag1(Y386_Y409~0) -> Pag1(Y386_Y409~P)

Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 0 P Y386_Y409 0 P take all branches, once each, in any order⬇⬇

Pag1(Y386_Y409~P) -> Pag1(Y386_Y409~0)

Pag1 PRS1 Y165_Y183 0 P PRS2 Y317 0 P Y386_Y409 0 P take one or more branches, once each, in any order⬆⬆

Gab2(Y441~0) -> Gab2(Y441~P)

Gab2 PRS Y441 0 P take all branches, once each, in any order⬇⬇

Gab2(Y441~P) -> Gab2(Y441~0)

Gab2 PRS Y441 0 P take one or more branches, once each, in any order⬆⬆

Lat(Y136~0) -> Lat(Y136~P)

Lat Y136 0 P take all branches, once each, in any order⬇⬇ Y175 0 P

Lat(Y136~P) -> Lat(Y136~0)

Lat Y136 0 P take one or more branches, once each, in any order⬆⬆ Y175 0 P

Lat(Y175~0) -> Lat(Y175~P)

Lat Y136 0 P Y175 0 P take all branches, once each, in any order⬇⬇

Lat(Y175~P) -> Lat(Y175~0)

Lat Y136 0 P Y175 0 P take one or more branches, once each, in any order⬆⬆

Plcg1(Y783~0) -> Plcg1(Y783~P)

Plcg1 SH2 SH3 PLC Y783 0 P take all branches, once each, in any order⬇⬇

Plcg1(Y783~P) -> Plcg1(Y783~0)

Plcg1 SH2 SH3 PLC Y783 0 P take one or more branches, once each, in any order⬆⬆