Molecules

egf(r)

egf r

egfr(l,r,Y1068~Y~pY,Y1148~Y~pY)

egfr l r Y1068 Y pY Y1148 Y pY

Shc(PTB,Y317~Y~pY)

Shc PTB Y317 Y pY

Grb2(SH2,SH3)

Grb2 SH2 SH3

Sos(dom)

Sos dom

Species

egf(r)

egf r

Grb2(SH2,SH3)

Grb2 SH2 SH3

Shc(PTB,Y317~Y)

Shc PTB Y317 Y

Sos(dom)

Sos dom

egfr(l,r,Y1068~Y,Y1148~Y)

egfr l r Y1068 Y Y1148 Y

Grb2(SH2,SH3!1).Sos(dom!1)

Grb2 SH2 1SH3 Sos 1dom

Observables

egfr.egfr

egfr l r Y1068 Y pY Y1148 Y pY egfr l r Y1068 Y pY Y1148 Y pY

Shc(PTB!+,Y317~pY!2).Grb2(SH2!2,SH3!3).Sos(dom!3)

Shc PTB Y317 2pY Grb2 2SH2 3SH3 Sos 3dom

egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2)

egfr l r Y1068 1pY Y1148 Y pY Grb2 1SH2 2SH3 Sos 2dom

egfr(Y1068~pY!?)

egfr l r Y1068 pY Y1148 Y pY

egfr(Y1148~pY!?)

egfr l r Y1068 Y pY Y1148 pY

Shc(Y317~pY!1).Grb2(SH2!1)

Shc PTB Y317 1pY Grb2 1SH2 SH3

Shc(Y317~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2)

Shc PTB Y317 1pY Grb2 1SH2 2SH3 Sos 2dom

egfr(Y1068~pY!1).Grb2(SH2!1)

egfr l r Y1068 1pY Y1148 Y pY Grb2 1SH2 SH3

egfr(Y1148~pY!1).Shc(PTB!1,Y317~Y)

egfr l r Y1068 Y pY Y1148 1pY Shc 1PTB Y317 Y

egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY!?)

egfr l r Y1068 Y pY Y1148 1pY Shc 1PTB Y317 pY

Shc(Y317~pY!?)

Shc PTB Y317 pY

egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2)

egfr l r Y1068 1pY Y1148 Y pY Grb2 1SH2 2SH3 Sos 2dom
Strong differences are seen for R_G_S in comparison with path model

egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY!2).Grb2(SH2!2,SH3!3).Sos(dom!3)

egfr l r Y1068 Y pY Y1148 1pY Shc 1PTB Y317 2pY Grb2 2SH2 3SH3 Sos 3dom

egfr

egfr l r Y1068 Y pY Y1148 Y pY

Shc

Shc PTB Y317 Y pY

Sos

Sos dom

Grb2

Grb2 SH2 SH3

Reaction Rules

Ligand-receptor binding

egfr(l,r) + egf(r) <-> egfr(l!1,r).egf(r!1)

egfr 1 ⬆⬇l r Y1068 Y pY Y1148 Y pY egf 1 ⬆⬇r
Note changed multiplicityReceptor-aggregation

egfr(l!+,r) + egfr(l!+,r) <-> egfr(l!+,r!3).egfr(l!+,r!3)

egfr l 3 ⬆⬇r Y1068 Y pY Y1148 Y pY egfr l 3 ⬆⬇r Y1068 Y pY Y1148 Y pY
Transphosphorylation of egfr by RTK

egfr(r!+,Y1068~Y) -> egfr(r!+,Y1068~pY)

egfr l r Y1068 Y pY take all branches, once each, in any order⬇⬇ Y1148 Y pY

egfr(r!+,Y1148~Y) -> egfr(r!+,Y1148~pY)

egfr l r Y1068 Y pY Y1148 Y pY take all branches, once each, in any order⬇⬇
Dephosphorylayion

egfr(Y1068~pY) -> egfr(Y1068~Y)

egfr l r Y1068 Y pY take one or more branches, once each, in any order⬆⬆ Y1148 Y pY

egfr(Y1148~pY) -> egfr(Y1148~Y)

egfr l r Y1068 Y pY Y1148 Y pY take one or more branches, once each, in any order⬆⬆
Shc transphosph

egfr(r!+,Y1148~pY!1).Shc(PTB!1,Y317~Y) -> egfr(r!+,Y1148~pY!1).Shc(PTB!1,Y317~pY)

egfr l r Y1068 Y pY Y1148 1pY Shc 1PTB Y317 Y pY take all branches, once each, in any order⬇⬇

Shc(PTB!+,Y317~pY) -> Shc(PTB!+,Y317~Y)

Shc PTB Y317 Y pY take one or more branches, once each, in any order⬆⬆
Y1068 activity

egfr(Y1068~pY) + Grb2(SH2,SH3) <-> egfr(Y1068~pY!1).Grb2(SH2!1,SH3)

egfr l r Y1068 1 ⬆⬇pY Y1148 Y pY Grb2 1 ⬆⬇SH2 SH3

egfr(Y1068~pY) + Grb2(SH2,SH3!+) <-> egfr(Y1068~pY!1).Grb2(SH2!1,SH3!+)

egfr l r Y1068 1 ⬆⬇pY Y1148 Y pY Grb2 1 ⬆⬇SH2 SH3

egfr(Y1068~pY!1).Grb2(SH2!1,SH3) + Sos(dom) <-> egfr(Y1068~pY!1).Grb2(SH2!1,SH3!2).Sos(dom!2)

egfr l r Y1068 1pY Y1148 Y pY Grb2 1SH2 2 ⬆⬇SH3 Sos 2 ⬆⬇dom
Y1148 activity

egfr(Y1148~pY) + Shc(PTB,Y317~Y) <-> egfr(Y1148~pY!1).Shc(PTB!1,Y317~Y)

egfr l r Y1068 Y pY Y1148 1 ⬆⬇pY Shc 1 ⬆⬇PTB Y317 Y

egfr(Y1148~pY) + Shc(PTB,Y317~pY) <-> egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY)

egfr l r Y1068 Y pY Y1148 1 ⬆⬇pY Shc 1 ⬆⬇PTB Y317 pY

egfr(Y1148~pY) + Shc(PTB,Y317~pY!1).Grb2(SH2!1,SH3) <-> egfr(Y1148~pY!2).Shc(PTB!2,Y317~pY!1).Grb2(SH2!1,SH3)

egfr l r Y1068 Y pY Y1148 2 ⬆⬇pY Shc 2 ⬆⬇PTB Y317 1pY Grb2 1SH2 SH3

egfr(Y1148~pY) + Shc(PTB,Y317~pY!1).Grb2(SH2!1,SH3!3).Sos(dom!3) <-> egfr(Y1148~pY!2).Shc(PTB!2,Y317~pY!1).Grb2(SH2!1,SH3!3).Sos(dom!3)

egfr l r Y1068 Y pY Y1148 2 ⬆⬇pY Shc 2 ⬆⬇PTB Y317 1pY Grb2 1SH2 3SH3 Sos 3dom

egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) + Grb2(SH2,SH3) <-> egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY!2).Grb2(SH2!2,SH3)

egfr l r Y1068 Y pY Y1148 1pY Shc 1PTB Y317 2 ⬆⬇pY Grb2 2 ⬆⬇SH2 SH3

egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY) + Grb2(SH2,SH3!3).Sos(dom!3) <-> egfr(Y1148~pY!1).Shc(PTB!1,Y317~pY!2).Grb2(SH2!2,SH3!3).Sos(dom!3)

egfr l r Y1068 Y pY Y1148 1pY Shc 1PTB Y317 2 ⬆⬇pY Grb2 2 ⬆⬇SH2 3SH3 Sos 3dom

Shc(PTB!+,Y317~pY!2).Grb2(SH2!2,SH3) + Sos(dom) <-> Shc(PTB!+,Y317~pY!2).Grb2(SH2!2,SH3!3).Sos(dom!3)

Shc PTB Y317 2pY Grb2 2SH2 3 ⬆⬇SH3 Sos 3 ⬆⬇dom
Cytosolic

Shc(PTB,Y317~pY) + Grb2(SH2,SH3) <-> Shc(PTB,Y317~pY!1).Grb2(SH2!1,SH3)

Shc PTB Y317 1 ⬆⬇pY Grb2 1 ⬆⬇SH2 SH3

Shc(PTB,Y317~pY) + Grb2(SH2,SH3!+) <-> Shc(PTB,Y317~pY!1).Grb2(SH2!1,SH3!+)

Shc PTB Y317 1 ⬆⬇pY Grb2 1 ⬆⬇SH2 SH3

Shc(PTB,Y317~pY) -> Shc(PTB,Y317~Y)

Shc PTB Y317 Y pY take one or more branches, once each, in any order⬆⬆

Grb2(SH2,SH3) + Sos(dom) <-> Grb2(SH2,SH3!1).Sos(dom!1)

Grb2 SH2 1 ⬆⬇SH3 Sos 1 ⬆⬇dom

Shc(PTB,Y317~pY!2).Grb2(SH2!2,SH3) + Sos(dom) <-> Shc(PTB,Y317~pY!2).Grb2(SH2!2,SH3!3).Sos(dom!3)

Shc PTB Y317 2pY Grb2 2SH2 3 ⬆⬇SH3 Sos 3 ⬆⬇dom