Molecules


The molecule types are illustrated by nested boxes in Fig. 1
B cell antigen receptor
Y188 and Y199 in the Ig-alpha ITAM are lumped together
Y196 and Y207 in the Ig-beta ITAM are lumped together
0, unphosphorylated; P, singly phosphorylated; PP, doubly phosphorylated

BCR(Y188_Y199~0~P~PP,Y196_Y207~0~P~PP)

BCR Y188_Y199 0 P PP Y196_Y207 0 P PP

Src-family kinase Lyn
Y397, A-loop tyrosine
Y508, C-terminal regulatory tyrosine
0, unphosphorylated; P, phosphorylated

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

Lyn unique SH3 SH2 Y397 0 P Y508 0 P

Src-family kinase Fyn (FynT isoform)
Y420, A-loop tyrosine
Y531, C-terminal regulatory tyrosine
0, unphosphorylated; P, phosphorylated

Fyn(unique,SH3,SH2,Y420~0~P,Y531~0~P)

Fyn unique SH3 SH2 Y420 0 P Y531 0 P

Protein tyrosine kinase Csk

Csk(SH2)

Csk SH2

Adapter protein PAG (aka Cbp)
PRS1, proline-rich sequence recognized by SH3 domain of Fyn
PRS2, proline-rich sequence recognized by SH3 domain of Lyn
Y163 and Y181 are lumped together (docking sites for SH2 domain of Fyn)
Y387 and Y417 are lumped together (docking sites for SH2 domain of Lyn)
Y317, docking site of Csk
0, unphosphorylated; P, phosphorylated

PAG(PRS1,PRS2,Y317~0~P,Y163_Y181~0~P,Y387_Y417~0~P)

PAG PRS1 PRS2 Y317 0 P Y163_Y181 0 P Y387_Y417 0 P

Protein tyrosine kinase Syk
tSH2, the tandem SH2 domains of Syk are lumped together
Y525 and Y526 in the activation loop of Syk are lumped together

Syk(tSH2,Y525_Y526~0~P)

Syk tSH2 Y525_Y526 0 P

Species

BCR(Y188_Y199~0,Y196_Y207~0)

BCR Y188_Y199 0 Y196_Y207 0

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

Lyn unique SH3 SH2 Y397 0 Y508 0

Fyn(unique,SH3,SH2,Y420~0,Y531~0)

Fyn unique SH3 SH2 Y420 0 Y531 0

PAG(PRS1,PRS2,Y317~0,Y163_Y181~0,Y387_Y417~0)

PAG PRS1 PRS2 Y317 0 Y163_Y181 0 Y387_Y417 0

Csk(SH2)

Csk SH2

Syk(tSH2,Y525_Y526~0)

Syk tSH2 Y525_Y526 0

Observables

Activated_Syk Syk(Y525_Y526~P)

Syk ?tSH2 Y525_Y526 P

Ig_alpha_P BCR(Y188_Y199~P)

BCR Y188_Y199 P Y196_Y207 0 P ?PP

Ig_alpha_PP BCR(Y188_Y199~PP)

BCR Y188_Y199 PP Y196_Y207 0 P ?PP

Ig_beta_PP BCR(Y196_Y207~PP)

BCR Y188_Y199 0 P ?PP Y196_Y207 PP

Activated_Lyn Lyn(Y397~P)

Lyn ?unique ?SH3 ?SH2 Y397 P Y508 0 ?P

Autoinhibited_Lyn Lyn(Y508~P!+)

Lyn ?unique ?SH3 ?SH2 Y397 0 ?P Y508 P

Activated_Fyn Fyn(Y420~P)

Fyn ?unique ?SH3 ?SH2 Y420 P Y531 0 ?P

Autoinhibited_Fyn Fyn(Y531~P!+)

Fyn ?unique ?SH3 ?SH2 Y420 0 ?P Y531 P

PAG1_Csk PAG(Y317~P!+)

PAG ?PRS1 ?PRS2 Y317 P Y163_Y181 0 ?P Y387_Y417 0 ?P

Reaction Rules


The following 25 sets of rules are represented by Arrows 1-25 in Fig. 1
The rules within a set share a common reaction center
Arrow 1
unique domain of Lyn binds unphosphorylated Ig-alpha ITAM

BCR(Y188_Y199~0) + Lyn(unique,SH3,SH2) <-> BCR(Y188_Y199~0!1).Lyn(unique!1,SH3,SH2)

BCR Y188_Y199 ⬇⬆0 Y196_Y207 0 P ?PP ⬇⬆ Lyn ⬇⬆unique SH3 SH2 Y397 0 ?P Y508 0 ?P

Arrow 2
SH2 domain of Lyn binds phosphorylated Ig-alpha ITAM

BCR(Y188_Y199~P) + Lyn(unique,SH3,SH2) <-> BCR(Y188_Y199~P!1).Lyn(unique,SH3,SH2!1)

BCR Y188_Y199 ⬇⬆P Y196_Y207 0 P ?PP ⬇⬆ Lyn unique SH3 ⬇⬆SH2 Y397 0 ?P Y508 0 ?P

BCR(Y188_Y199~PP) + Lyn(unique,SH3,SH2) <-> BCR(Y188_Y199~PP!1).Lyn(unique,SH3,SH2!1)

BCR Y188_Y199 ⬇⬆PP Y196_Y207 0 P ?PP ⬇⬆ Lyn unique SH3 ⬇⬆SH2 Y397 0 ?P Y508 0 ?P

Arrow 3
autoinhibition of Lyn, SH2 domain of Lyn binds C-terminal pY

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

Lyn unique SH3 ⬇⬆SH2 Y397 0 ?P Y508 ⬇⬆P

Arrow 4
Lyn phosphorylates Ig-alpha ITAM

Lyn(Y397~0).BCR() + BCR(Y188_Y199~0) -> Lyn(Y397~0).BCR() + BCR(Y188_Y199~P)

Lyn ?unique ?SH3 ?SH2 Y397 0 Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P take all branches, once each, in any order⬇ Y196_Y207 0 P ?PP

Lyn(Y397~0).BCR() + BCR(Y188_Y199~P) -> Lyn(Y397~0).BCR() + BCR(Y188_Y199~PP)

Lyn ?unique ?SH3 ?SH2 Y397 0 Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 P PP take all branches, once each, in any order⬇ Y196_Y207 0 P ?PP

Lyn(Y397~P).BCR() + BCR(Y188_Y199~0) -> Lyn(Y397~P).BCR() + BCR(Y188_Y199~P)

Lyn ?unique ?SH3 ?SH2 Y397 P Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P take all branches, once each, in any order⬇ Y196_Y207 0 P ?PP

Lyn(Y397~P).BCR() + BCR(Y188_Y199~P) -> Lyn(Y397~P).BCR() + BCR(Y188_Y199~PP)

Lyn ?unique ?SH3 ?SH2 Y397 P Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 P PP take all branches, once each, in any order⬇ Y196_Y207 0 P ?PP

Arrow 5
Lyn phosphorylates Ig-beta ITAM

Lyn(Y397~0).BCR() + BCR(Y196_Y207~0) -> Lyn(Y397~0).BCR() + BCR(Y196_Y207~P)

Lyn ?unique ?SH3 ?SH2 Y397 0 Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P take all branches, once each, in any order⬇

Lyn(Y397~0).BCR() + BCR(Y196_Y207~P) -> Lyn(Y397~0).BCR() + BCR(Y196_Y207~PP)

Lyn ?unique ?SH3 ?SH2 Y397 0 Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 P PP take all branches, once each, in any order⬇

Lyn(Y397~P).BCR() + BCR(Y196_Y207~0) -> Lyn(Y397~P).BCR() + BCR(Y196_Y207~P)

Lyn ?unique ?SH3 ?SH2 Y397 P Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P take all branches, once each, in any order⬇

Lyn(Y397~P).BCR() + BCR(Y196_Y207~P) -> Lyn(Y397~P).BCR() + BCR(Y196_Y207~PP)

Lyn ?unique ?SH3 ?SH2 Y397 P Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 P PP take all branches, once each, in any order⬇

Arrow 6
trans autophosphorylation of Lyn
receptor-bound Lyn phosphorylates receptor-bound Lyn

Lyn(Y397~0).BCR() + BCR().Lyn(Y397~0) -> Lyn(Y397~0).BCR() + BCR().Lyn(Y397~P)

Lyn ?unique ?SH3 ?SH2 Y397 0 Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP Lyn ?unique ?SH3 ?SH2 Y397 0 P take all branches, once each, in any order⬇ Y508 0 ?P

Lyn(Y397~P).BCR() + BCR().Lyn(Y397~0) -> Lyn(Y397~P).BCR() + BCR().Lyn(Y397~P)

Lyn ?unique ?SH3 ?SH2 Y397 P Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP Lyn ?unique ?SH3 ?SH2 Y397 0 P take all branches, once each, in any order⬇ Y508 0 ?P

free Lyn phosphorylates free Lyn

Lyn(unique,SH3,SH2,Y397~0,Y508~0) + Lyn(unique,SH3,SH2,Y397~0,Y508~0) -> Lyn(unique,SH3,SH2,Y397~0,Y508~0) + Lyn(unique,SH3,SH2,Y397~P,Y508~0)

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

Lyn(unique,SH3,SH2,Y397~P,Y508~0) + Lyn(unique,SH3,SH2,Y397~0,Y508~0) -> Lyn(unique,SH3,SH2,Y397~P,Y508~0) + Lyn(unique,SH3,SH2,Y397~P,Y508~0)

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

Arrow 7
Lyn phosphorylates Fyn
receptor-bound Lyn phosphorylates receptor-bound Fyn

Lyn(Y397~0).BCR() + BCR().Fyn(Y420~0) -> Lyn(Y397~0).BCR() + BCR().Fyn(Y420~P)

Lyn ?unique ?SH3 ?SH2 Y397 0 Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP Fyn ?unique ?SH3 ?SH2 Y420 0 P take all branches, once each, in any order⬇ Y531 0 ?P

Lyn(Y397~P).BCR() + BCR().Fyn(Y420~0) -> Lyn(Y397~P).BCR() + BCR().Fyn(Y420~P)

Lyn ?unique ?SH3 ?SH2 Y397 P Y508 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP Fyn ?unique ?SH3 ?SH2 Y420 0 P take all branches, once each, in any order⬇ Y531 0 ?P

free Lyn phosphorylates free Fyn

Lyn(unique,SH3,SH2,Y397~0,Y508~0) + Fyn(unique,SH3,SH2,Y420~0,Y531~0) -> Lyn(unique,SH3,SH2,Y397~0,Y508~0) + Fyn(unique,SH3,SH2,Y420~P,Y531~0)

Lyn unique SH3 SH2 Y397 0 Y508 0 Fyn unique SH3 SH2 Y420 0 P take all branches, once each, in any order⬇ Y531 0

Lyn(unique,SH3,SH2,Y397~P,Y508~0) + Fyn(unique,SH3,SH2,Y420~0,Y531~0) -> Lyn(unique,SH3,SH2,Y397~P,Y508~0) + Fyn(unique,SH3,SH2,Y420~P,Y531~0)

Lyn unique SH3 SH2 Y397 P Y508 0 Fyn unique SH3 SH2 Y420 0 P take all branches, once each, in any order⬇ Y531 0

Arrow 8
Lyn phosphorylates PAG

Lyn(Y397~P,Y508).PAG(Y387_Y417~0) -> Lyn(Y397~P,Y508).PAG(Y387_Y417~P)

Lyn ?unique ?SH3 ?SH2 Y397 P Y508 PAG ?PRS1 ?PRS2 Y317 0 ?P Y163_Y181 0 ?P Y387_Y417 0 P take all branches, once each, in any order⬇

Lyn(SH2!1,Y397~P,Y508).PAG(Y163_Y181~0,Y387_Y417~P!1) -> Lyn(SH2!1,Y397~P,Y508).PAG(Y163_Y181~P,Y387_Y417~P!1)

Lyn ?unique ?SH3 SH2 Y397 P Y508 PAG ?PRS1 ?PRS2 Y317 0 ?P Y163_Y181 0 P take all branches, once each, in any order⬇ Y387_Y417 P

Lyn(SH2!1,Y397~P,Y508).PAG(Y317~0,Y387_Y417~P!1) -> Lyn(SH2!1,Y397~P,Y508).PAG(Y317~P,Y387_Y417~P!1)

Lyn ?unique ?SH3 SH2 Y397 P Y508 PAG ?PRS1 ?PRS2 Y317 0 P take all branches, once each, in any order⬇ Y163_Y181 0 ?P Y387_Y417 P

Arrow 9
unique domain of Fyn binds unphosphorylated Ig-alpha ITAM

BCR(Y188_Y199~0) + Fyn(unique,SH3,SH2) <-> BCR(Y188_Y199~0!1).Fyn(unique!1,SH3,SH2)

BCR Y188_Y199 ⬇⬆0 Y196_Y207 0 P ?PP ⬇⬆ Fyn ⬇⬆unique SH3 SH2 Y420 0 ?P Y531 0 ?P

Arrow 10
SH2 domain of Fyn binds phosphorylated Ig-alpha ITAM

BCR(Y188_Y199~P) + Fyn(unique,SH3,SH2) <-> BCR(Y188_Y199~P!1).Fyn(unique,SH3,SH2!1)

BCR Y188_Y199 ⬇⬆P Y196_Y207 0 P ?PP ⬇⬆ Fyn unique SH3 ⬇⬆SH2 Y420 0 ?P Y531 0 ?P

BCR(Y188_Y199~PP) + Fyn(unique,SH3,SH2) <-> BCR(Y188_Y199~PP!1).Fyn(unique,SH3,SH2!1)

BCR Y188_Y199 ⬇⬆PP Y196_Y207 0 P ?PP ⬇⬆ Fyn unique SH3 ⬇⬆SH2 Y420 0 ?P Y531 0 ?P

Arrow 11
autoinhibition of Fyn, SH2 domain of Fyn binds C-terminal pY

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

Fyn unique SH3 ⬇⬆SH2 Y420 0 ?P Y531 ⬇⬆P

Arrow 12
Fyn phosphorylates Ig-beta ITAM

Fyn(Y420~0).BCR() + BCR(Y196_Y207~0) -> Fyn(Y420~0).BCR() + BCR(Y196_Y207~P)

Fyn ?unique ?SH3 ?SH2 Y420 0 Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P take all branches, once each, in any order⬇

Fyn(Y420~0).BCR() + BCR(Y196_Y207~P) -> Fyn(Y420~0).BCR() + BCR(Y196_Y207~PP)

Fyn ?unique ?SH3 ?SH2 Y420 0 Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 P PP take all branches, once each, in any order⬇

Fyn(Y420~P).BCR() + BCR(Y196_Y207~0) -> Fyn(Y420~P).BCR() + BCR(Y196_Y207~P)

Fyn ?unique ?SH3 ?SH2 Y420 P Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P take all branches, once each, in any order⬇

Fyn(Y420~P).BCR() + BCR(Y196_Y207~P) -> Fyn(Y420~P).BCR() + BCR(Y196_Y207~PP)

Fyn ?unique ?SH3 ?SH2 Y420 P Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 P PP take all branches, once each, in any order⬇

Arrow 13
Fyn phosphorylates Ig-alpha ITAM

Fyn(Y420~0).BCR() + BCR(Y188_Y199~0) -> Fyn(Y420~0).BCR() + BCR(Y188_Y199~P)

Fyn ?unique ?SH3 ?SH2 Y420 0 Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P take all branches, once each, in any order⬇ Y196_Y207 0 P ?PP

Fyn(Y420~0).BCR() + BCR(Y188_Y199~P) -> Fyn(Y420~0).BCR() + BCR(Y188_Y199~PP)

Fyn ?unique ?SH3 ?SH2 Y420 0 Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 P PP take all branches, once each, in any order⬇ Y196_Y207 0 P ?PP

Fyn(Y420~P).BCR() + BCR(Y188_Y199~0) -> Fyn(Y420~P).BCR() + BCR(Y188_Y199~P)

Fyn ?unique ?SH3 ?SH2 Y420 P Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P take all branches, once each, in any order⬇ Y196_Y207 0 P ?PP

Fyn(Y420~P).BCR() + BCR(Y188_Y199~P) -> Fyn(Y420~P).BCR() + BCR(Y188_Y199~PP)

Fyn ?unique ?SH3 ?SH2 Y420 P Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 P PP take all branches, once each, in any order⬇ Y196_Y207 0 P ?PP

Arrow 14
trans autophosphorylation of Fyn
receptor-bound Fyn phosphorylates receptor-bound Fyn

Fyn(Y420~0).BCR() + BCR().Fyn(Y420~0) -> Fyn(Y420~0).BCR() + BCR().Fyn(Y420~P)

Fyn ?unique ?SH3 ?SH2 Y420 0 Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP Fyn ?unique ?SH3 ?SH2 Y420 0 P take all branches, once each, in any order⬇ Y531 0 ?P

Fyn(Y420~P).BCR() + BCR().Fyn(Y420~0) -> Fyn(Y420~P).BCR() + BCR().Fyn(Y420~P)

Fyn ?unique ?SH3 ?SH2 Y420 P Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP Fyn ?unique ?SH3 ?SH2 Y420 0 P take all branches, once each, in any order⬇ Y531 0 ?P

free Fyn phosphorylates free Fyn

Fyn(unique,SH3,SH2,Y420~0,Y531~0) + Fyn(unique,SH3,SH2,Y420~0,Y531~0) -> Fyn(unique,SH3,SH2,Y420~0,Y531~0) + Fyn(unique,SH3,SH2,Y420~P,Y531~0)

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

Fyn(unique,SH3,SH2,Y420~P,Y531~0) + Fyn(unique,SH3,SH2,Y420~0,Y531~0) -> Fyn(unique,SH3,SH2,Y420~P,Y531~0) + Fyn(unique,SH3,SH2,Y420~P,Y531~0)

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

Arrow 15
Fyn phosphorylates Lyn
receptor-bound Fyn phosphorylates receptor-bound Lyn

Fyn(Y420~0).BCR() + BCR().Lyn(Y397~0) -> Fyn(Y420~0).BCR() + BCR().Lyn(Y397~P)

Fyn ?unique ?SH3 ?SH2 Y420 0 Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP Lyn ?unique ?SH3 ?SH2 Y397 0 P take all branches, once each, in any order⬇ Y508 0 ?P

Fyn(Y420~P).BCR() + BCR().Lyn(Y397~0) -> Fyn(Y420~P).BCR() + BCR().Lyn(Y397~P)

Fyn ?unique ?SH3 ?SH2 Y420 P Y531 0 ?P BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP BCR Y188_Y199 0 P ?PP Y196_Y207 0 P ?PP Lyn ?unique ?SH3 ?SH2 Y397 0 P take all branches, once each, in any order⬇ Y508 0 ?P

free Fyn phosphorylates free Lyn

Fyn(unique,SH3,SH2,Y420~0,Y531~0) + Lyn(unique,SH3,SH2,Y397~0,Y508~0) -> Fyn(unique,SH3,SH2,Y420~0,Y531~0) + Lyn(unique,SH3,SH2,Y397~P,Y508~0)

Fyn unique SH3 SH2 Y420 0 Y531 0 Lyn unique SH3 SH2 Y397 0 P take all branches, once each, in any order⬇ Y508 0

Fyn(unique,SH3,SH2,Y420~P,Y531~0) + Lyn(unique,SH3,SH2,Y397~0,Y508~0) -> Fyn(unique,SH3,SH2,Y420~P,Y531~0) + Lyn(unique,SH3,SH2,Y397~P,Y508~0)

Fyn unique SH3 SH2 Y420 P Y531 0 Lyn unique SH3 SH2 Y397 0 P take all branches, once each, in any order⬇ Y508 0

Arrow 16
Fyn phosphorylates PAG

Fyn(SH2!1,Y420~P,Y531).PAG(Y163_Y181~P!1,Y387_Y417~0) -> Fyn(SH2!1,Y420~P,Y531).PAG(Y163_Y181~P!1,Y387_Y417~P)

Fyn ?unique ?SH3 SH2 Y420 P Y531 PAG ?PRS1 ?PRS2 Y317 0 ?P Y163_Y181 P Y387_Y417 0 P take all branches, once each, in any order⬇

Fyn(Y420~P,Y531).PAG(Y163_Y181~0) -> Fyn(Y420~P,Y531).PAG(Y163_Y181~P)

Fyn ?unique ?SH3 ?SH2 Y420 P Y531 PAG ?PRS1 ?PRS2 Y317 0 ?P Y163_Y181 0 P take all branches, once each, in any order⬇ Y387_Y417 0 ?P

Fyn(SH2!1,Y420~P,Y531).PAG(Y163_Y181~P!1,Y317~0) -> Fyn(SH2!1,Y420~P,Y531).PAG(Y163_Y181~P!1,Y317~P)

Fyn ?unique ?SH3 SH2 Y420 P Y531 PAG ?PRS1 ?PRS2 Y317 0 P take all branches, once each, in any order⬇ Y163_Y181 P Y387_Y417 0 ?P

Arrow 17
tandem SH2 domains of Syk bind doubly phosphorylated Ig-beta ITAM

Syk(tSH2) + BCR(Y196_Y207~PP) <-> Syk(tSH2!1).BCR(Y196_Y207~PP!1)

Syk ⬇⬆tSH2 Y525_Y526 0 ?P ⬇⬆ BCR Y188_Y199 0 P ?PP Y196_Y207 ⬇⬆PP

Arrow 18
trans autophosphorylation of receptor-bound Syk

Syk(tSH2!+,Y525_Y526~0) + Syk(tSH2!+,Y525_Y526~0) -> Syk(tSH2!+,Y525_Y526~0) + Syk(tSH2!+,Y525_Y526~P)

Syk tSH2 Y525_Y526 0 Syk tSH2 Y525_Y526 0 P take all branches, once each, in any order⬇

Syk(tSH2!+,Y525_Y526~P) + Syk(tSH2!+,Y525_Y526~0) -> Syk(tSH2!+,Y525_Y526~P) + Syk(tSH2!+,Y525_Y526~P)

Syk tSH2 Y525_Y526 P Syk tSH2 Y525_Y526 0 P take all branches, once each, in any order⬇

Arrow 19
SH3 domain of Lyn binds PRS2 in PAG
association, Lyn is free

Lyn(unique,SH3,SH2) + PAG(PRS2,Y387_Y417) -> Lyn(unique,SH3!1,SH2).PAG(PRS2!1,Y387_Y417)

Lyn unique ⬇SH3 SH2 Y397 0 ?P Y508 0 ?P ⬇ PAG ?PRS1 ⬇PRS2 Y317 0 ?P Y163_Y181 0 ?P Y387_Y417

dissociation

Lyn(unique,SH3!1,SH2).PAG(PRS2!1,Y387_Y417) -> Lyn(unique,SH3,SH2) + PAG(PRS2,Y387_Y417)

Lyn unique ⬆SH3 SH2 Y397 0 ?P Y508 0 ?P ⬆ PAG ?PRS1 ⬆PRS2 Y317 0 ?P Y163_Y181 0 ?P Y387_Y417

association, Lyn is tethered to PAG (via SH2 domain-pY interaction)
Lyn, already tethered in PAG by SH2, binds PAG via SH3 domain

Lyn(unique,SH3,SH2!2).PAG(PRS2,Y387_Y417~P!2) -> Lyn(unique,SH3!1,SH2!2).PAG(PRS2!1,Y387_Y417~P!2)

Lyn unique ⬇SH3 SH2 Y397 0 ?P Y508 0 ?P PAG ?PRS1 ⬇PRS2 Y317 0 ?P Y163_Y181 0 ?P Y387_Y417 P

Arrow 20
SH2 domain of Lyn binds a pY docking site in PAG
association, Lyn is free

Lyn(unique,SH3,SH2) + PAG(PRS2,Y387_Y417~P) -> Lyn(unique,SH3,SH2!2).PAG(PRS2,Y387_Y417~P!2)

Lyn unique SH3 ⬇SH2 Y397 0 ?P Y508 0 ?P ⬇ PAG ?PRS1 PRS2 Y317 0 ?P Y163_Y181 0 ?P Y387_Y417 ⬇P

association, Lyn is tethered to PAG (via SH3 domain-PRS interaction)

Lyn(unique,SH3!1,SH2).PAG(PRS2!1,Y387_Y417~P) -> Lyn(unique,SH3!1,SH2!2).PAG(PRS2!1,Y387_Y417~P!2)

Lyn unique SH3 ⬇SH2 Y397 0 ?P Y508 0 ?P PAG ?PRS1 PRS2 Y317 0 ?P Y163_Y181 0 ?P Y387_Y417 ⬇P

release, breaking two-point attachment

Lyn(unique,SH3!1,SH2!2).PAG(PRS2!1,Y387_Y417~P!2) -> Lyn(unique,SH3,SH2) + PAG(PRS2,Y387_Y417~P)

Lyn unique ⬆SH3 ⬆SH2 Y397 0 ?P Y508 0 ?P ⬆ PAG ?PRS1 ⬆PRS2 Y317 0 ?P Y163_Y181 0 ?P Y387_Y417 ⬆P

Arrow 21
SH3 domain of Fyn binds PRS1 in PAG
association, Fyn is free

Fyn(unique,SH3,SH2) + PAG(PRS1,Y163_Y181) -> Fyn(unique,SH3!1,SH2).PAG(PRS1!1,Y163_Y181)

Fyn unique ⬇SH3 SH2 Y420 0 ?P Y531 0 ?P ⬇ PAG ⬇PRS1 ?PRS2 Y317 0 ?P Y163_Y181 Y387_Y417 0 ?P

dissociation

Fyn(unique,SH3!1,SH2).PAG(PRS1!1,Y163_Y181) -> Fyn(unique,SH3,SH2) + PAG(PRS1,Y163_Y181)

Fyn unique ⬆SH3 SH2 Y420 0 ?P Y531 0 ?P ⬆ PAG ⬆PRS1 ?PRS2 Y317 0 ?P Y163_Y181 Y387_Y417 0 ?P

association, Fyn is tethered to PAG (via SH2 domain-pY interaction)

Fyn(unique,SH3,SH2!2).PAG(PRS1,Y163_Y181~P!2) -> Fyn(unique,SH3!1,SH2!2).PAG(PRS1!1,Y163_Y181~P!2)

Fyn unique ⬇SH3 SH2 Y420 0 ?P Y531 0 ?P PAG ⬇PRS1 ?PRS2 Y317 0 ?P Y163_Y181 P Y387_Y417 0 ?P

Arrow 22
SH2 domain of Fyn binds a pY docking site in PAG
association, Fyn is free

Fyn(unique,SH3,SH2) + PAG(PRS1,Y163_Y181~P) -> Fyn(unique,SH3,SH2!2).PAG(PRS1,Y163_Y181~P!2)

Fyn unique SH3 ⬇SH2 Y420 0 ?P Y531 0 ?P ⬇ PAG PRS1 ?PRS2 Y317 0 ?P Y163_Y181 ⬇P Y387_Y417 0 ?P

association, Fyn is tethered to PAG (via SH3 domain-PRS interaction)

Fyn(unique,SH3!1,SH2).PAG(PRS1!1,Y163_Y181~P) -> Fyn(unique,SH3!1,SH2!2).PAG(PRS1!1,Y163_Y181~P!2)

Fyn unique SH3 ⬇SH2 Y420 0 ?P Y531 0 ?P PAG PRS1 ?PRS2 Y317 0 ?P Y163_Y181 ⬇P Y387_Y417 0 ?P

release, breaking two-point attachment

Fyn(unique,SH3!1,SH2!2).PAG(PRS1!1,Y163_Y181~P!2) -> Fyn(unique,SH3,SH2) + PAG(PRS1,Y163_Y181~P)

Fyn unique ⬆SH3 ⬆SH2 Y420 0 ?P Y531 0 ?P ⬆ PAG ⬆PRS1 ?PRS2 Y317 0 ?P Y163_Y181 ⬆P Y387_Y417 0 ?P

Arrow 23
SH2 domain of Csk binds pY317 docking site in PAG

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

Csk ⬇⬆SH2 ⬇⬆ PAG ?PRS1 ?PRS2 Y317 ⬇⬆P Y163_Y181 0 ?P Y387_Y417 0 ?P

Arrow 24
Csk cis phosphorylates C-terminal Y in Lyn

Lyn(Y508~0).PAG().Csk() -> Lyn(Y508~P).PAG().Csk()

Lyn ?unique ?SH3 ?SH2 Y397 0 ?P Y508 0 P take all branches, once each, in any order⬇ PAG ?PRS1 ?PRS2 Y317 0 ?P Y163_Y181 0 ?P Y387_Y417 0 ?P Csk ?SH2

Arrow 25
Csk cis phosphorylates C-terminal Y in Fyn

Fyn(Y531~0).PAG().Csk() -> Fyn(Y531~P).PAG().Csk()

Fyn ?unique ?SH3 ?SH2 Y420 0 ?P Y531 0 P take all branches, once each, in any order⬇ PAG ?PRS1 ?PRS2 Y317 0 ?P Y163_Y181 0 ?P Y387_Y417 0 ?P Csk ?SH2

The following rules are NOT illustrated in Fig. 1
Dephosphorylation of Ig-alpha

BCR(Y188_Y199~P) -> BCR(Y188_Y199~0)

BCR Y188_Y199 0 P take one or more branches, once each, in any order⬆ Y196_Y207 0 P ?PP

BCR(Y188_Y199~PP) -> BCR(Y188_Y199~P)

BCR Y188_Y199 P PP take one or more branches, once each, in any order⬆ Y196_Y207 0 P ?PP

Dephosphorylation of Ig-beta

BCR(Y196_Y207~P) -> BCR(Y196_Y207~0)

BCR Y188_Y199 0 P ?PP Y196_Y207 0 P take one or more branches, once each, in any order⬆

BCR(Y196_Y207~PP) -> BCR(Y196_Y207~P)

BCR Y188_Y199 0 P ?PP Y196_Y207 P PP take one or more branches, once each, in any order⬆

Dephosphorylation of Lyn

Lyn(Y397~P) -> Lyn(Y397~0)

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

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

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

Dephosphorylation of Fyn

Fyn(Y420~P) -> Fyn(Y420~0)

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

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

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

Dephosphorylation of PAG

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

PAG ?PRS1 ?PRS2 Y317 0 P take one or more branches, once each, in any order⬆ Y163_Y181 0 ?P Y387_Y417 0 ?P

PAG(Y387_Y417~P) -> PAG(Y387_Y417~0)

PAG ?PRS1 ?PRS2 Y317 0 ?P Y163_Y181 0 ?P Y387_Y417 0 P take one or more branches, once each, in any order⬆

PAG(Y163_Y181~P) -> PAG(Y163_Y181~0)

PAG ?PRS1 ?PRS2 Y317 0 ?P Y163_Y181 0 P take one or more branches, once each, in any order⬆ Y387_Y417 0 ?P

Dephosphorylation of Syk

Syk(Y525_Y526~P) -> Syk(Y525_Y526~0)

Syk ?tSH2 Y525_Y526 0 P take one or more branches, once each, in any order⬆