Molecules

EGF(rec)

EGF rec

EGFR(back,lig,cd~c~o,Y~u~p)

EGFR back lig cd c o Y u p

Grb2(SH2)

Grb2 SH2

Species

EGF(rec)

EGF rec

EGFR(back,lig,cd~c,Y~u)

EGFR back lig cd c Y u

Grb2(SH2)

Grb2 SH2

Observables


Unbound EGF

EGFfree EGF(rec)

EGF rec

Ligand-free EGFR

EGFRfree EGFR(lig)

EGFR ?back lig cd c ?o Y u ?p

Clusters
EGFR monomer
EGFR dimer
EGFR trimer
EGFR tetramer
Phosphorylated-EGFR

pEGFR EGFR(Y~p!?)

EGFR ?back ?lig cd c ?o Y ?p

Grb2

Grb2_pEGFR EGFR(Y~p!1).Grb2(SH2!1)

EGFR ?back ?lig cd c ?o Y p Grb2 SH2

Free Grb2

Grb2Free Grb2(SH2)

Grb2 SH2

Grb2-EGFR monomer

Grb2EGFRMonomer EGFR(cd,back,Y~p!1).Grb2(SH2!1)

EGFR back ?lig cd Y p Grb2 SH2

Grb2-EGFR dimer

Grb2EGFRDimer1 EGFR(cd,back!1,Y~p!2).Grb2(SH2!2).EGFR(cd,back!1,Y)

EGFR back ?lig cd Y p Grb2 SH2 EGFR back ?lig cd Y

Grb2EGFRDimer2 EGFR(cd~o!1,back,Y~p!2).Grb2(SH2!2).EGFR(cd~o!1,back,Y)

EGFR back ?lig cd o Y p Grb2 SH2 EGFR back ?lig cd o Y

Grb2EGFRDimer3 EGFR(cd,back!1,Y~p!2).Grb2(SH2!2).EGFR(cd,back!1,Y~p!3).Grb2(SH2!3)

EGFR back ?lig cd Y p Grb2 SH2 EGFR back ?lig cd Y p Grb2 SH2

Grb2EGFRDimer4 EGFR(cd~o!1,back,Y~p!2).Grb2(SH2!2).EGFR(cd~o!1,back,Y~p!3).Grb2(SH2!3)

EGFR back ?lig cd o Y p Grb2 SH2 EGFR back ?lig cd o Y p Grb2 SH2

Reaction Rules


EGF binding to EGFR not crosslinked via the ectodomain.

EGF(rec) + EGFR(back,lig) <-> EGF(rec!1).EGFR(back,lig!1)

EGF ⬇⬆rec ⬇⬆ EGFR back ⬇⬆lig cd c ?o Y u ?p

EGF binding to EGFR that is crosslinked via the ectodomain to a second EGFR and both crosslinked EGFR are free of EGF.

EGF(rec) + EGFR(back!1,lig).EGFR(back!1,lig) <-> EGF(rec!2).EGFR(back!1,lig!2).EGFR(back!1,lig)

EGF ⬇⬆rec ⬇⬆ EGFR back ⬇⬆lig cd c ?o Y u ?p EGFR back lig cd c ?o Y u ?p

EGF binding to EGFR that is crosslinked via the ectodomain to a second EGFR and the second EGFR is bound to EGF.

EGF(rec) + EGF(rec!1).EGFR(back!2,lig!1).EGFR(back!2,lig) <-> EGF(rec!3).EGF(rec!1).EGFR(back!2,lig!1).EGFR(back!2,lig!3)

EGF ⬇⬆rec ⬇⬆ EGF rec EGFR back lig cd c ?o Y u ?p EGFR back ⬇⬆lig cd c ?o Y u ?p

Ectodomain-ectodomain crosslinking of two EGFR that are not tethered and both EGFR are free of EGF.

EGFR(back,lig) + EGFR(back,lig) <-> EGFR(back!1,lig).EGFR(back!1,lig)

EGFR ⬇⬆back lig cd c ?o Y u ?p ⬇⬆ EGFR ⬇⬆back lig cd c ?o Y u ?p

Ectodomain-ectodomain crosslinking of two EGFR that are not tethered and only one EGFR is free of EGF.

EGFR(back,lig) + EGF(rec!1).EGFR(back,lig!1) <-> EGFR(back!2,lig).EGF(rec!1).EGFR(back!2,lig!1)

EGFR ⬇⬆back lig cd c ?o Y u ?p ⬇⬆ EGF rec EGFR ⬇⬆back lig cd c ?o Y u ?p

Ectodomain-ectodomain crosslinking of two EGFR that are not tethered and both EGFR are occupied by EGF.

EGF(rec!1).EGFR(back,lig!1) + EGF(rec!2).EGFR(back,lig!2) <-> EGF(rec!1).EGFR(back!3,lig!1).EGF(rec!2).EGFR(back!3,lig!2)

EGF rec EGFR ⬇⬆back lig cd c ?o Y u ?p ⬇⬆ EGF rec EGFR ⬇⬆back lig cd c ?o Y u ?p

Ectodomain-ectodomain crosslinking of two EGFR that are tethered and both EGFR are free of EGF (ring-closure reaction)

EGFR(cd~o!4,back,lig).EGFR(cd~o!2,back,lig).EGFR(cd~o!2,back!3).EGFR(cd~o!4,back!3) <-> EGFR(cd~o!4,back!1,lig).EGFR(cd~o!2,back!1,lig).EGFR(cd~o!2,back!3).EGFR(cd~o!4,back!3)

EGFR ⬇⬆back lig cd o Y u ?p EGFR ⬇⬆back lig cd o Y u ?p EGFR back ?lig cd o Y u ?p EGFR back ?lig cd o Y u ?p

Ectodomain-ectodomain crosslinking of two EGFR that are tethered and only one EGFR is free of EGF (ring-closure reaction)

EGFR(cd~o!4,back,lig).EGFR(cd~o!2,back,lig!+).EGFR(cd~o!2,back!3).EGFR(cd~o!4,back!3) <-> EGFR(cd~o!4,back!1,lig).EGFR(cd~o!2,back!1,lig!+).EGFR(cd~o!2,back!3).EGFR(cd~o!4,back!3)

EGFR ⬇⬆back lig cd o Y u ?p EGFR ⬇⬆back lig cd o Y u ?p EGFR back ?lig cd o Y u ?p EGFR back ?lig cd o Y u ?p

Ectodomain-ectodomain crosslinking of two EGFR that are tethered and both EGFR are occuplied by EGF (ring-closure reaction)

EGFR(cd~o!4,back,lig!+).EGFR(cd~o!2,back,lig!+).EGFR(cd~o!2,back!3).EGFR(cd~o!4,back!3) <-> EGFR(cd~o!4,back!1,lig!+).EGFR(cd~o!2,back!1,lig!+).EGFR(cd~o!2,back!3).EGFR(cd~o!4,back!3)

EGFR ⬇⬆back lig cd o Y u ?p EGFR ⬇⬆back lig cd o Y u ?p EGFR back ?lig cd o Y u ?p EGFR back ?lig cd o Y u ?p

EGF-induced activating conformation change of EGFR cytosolic tail

EGFR(lig!+,cd~c) -> EGFR(lig!+,cd~o)

EGFR ?back lig cd c o take all branches, once each, in any order⬇ Y u ?p

EGF-independent deactivating conformatoin change of EGFR cytosolic tail

EGFR(cd~o) -> EGFR(cd~c)

EGFR ?back ?lig cd c o take one or more branches, once each, in any order⬆ Y u ?p

Crosslinking of conformationally-modified cytosolic tails of EGFR that are not tethered

EGFR(cd~o) + EGFR(cd~o) <-> EGFR(cd~o!1).EGFR(cd~o!1)

EGFR ?back ?lig cd ⬇⬆o Y u ?p ⬇⬆ EGFR ?back ?lig cd ⬇⬆o Y u ?p

Crosslinking of conformationally-modified cytosolic tails of EGFR that are tethered (ring-closure reaction)

EGFR(cd~o,back!1).EGFR(cd~o!3,back!1).EGFR(cd~o!3,back!2).EGFR(cd~o,back!2) <-> EGFR(cd~o!4,back!1).EGFR(cd~o!3,back!1).EGFR(cd~o!3,back!2).EGFR(cd~o!4,back!2)

EGFR back ?lig cd ⬇⬆o Y u ?p EGFR back ?lig cd o Y u ?p EGFR back ?lig cd o Y u ?p EGFR back ?lig cd ⬇⬆o Y u ?p

EGFR phosphorylation

EGFR(cd~o!1).EGFR(cd~o!1,Y~u) -> EGFR(cd~o!1).EGFR(cd~o!1,Y~p)

EGFR ?back ?lig cd o Y u ?p EGFR ?back ?lig cd o Y u p take all branches, once each, in any order⬇

EGFR dephosphorylation

EGFR(Y~p) -> EGFR(Y~u)

EGFR ?back ?lig cd c ?o Y u p take one or more branches, once each, in any order⬆

Grb2 binds phosphorylated receptor

Grb2(SH2) + EGFR(Y~p) <-> Grb2(SH2!1).EGFR(Y~p!1)

Grb2 ⬇⬆SH2 ⬇⬆ EGFR ?back ?lig cd c ?o Y ⬇⬆p