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

EGF(rec)

EGF rec
Ligand-free EGFR

EGFR(lig)

EGFR back lig cd c o Y u p
ClustersEGFR monomerEGFR dimerEGFR trimerEGFR tetramerPhosphorylated-EGFR

EGFR(Y~p!?)

EGFR back lig cd c o Y p
Grb2

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

EGFR back lig cd c o Y 1p Grb2 1SH2
Free Grb2

Grb2(SH2)

Grb2 SH2
Grb2-EGFR monomer

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

EGFR back lig cd Y 1p Grb2 1SH2
Grb2-EGFR dimer

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

EGFR 1back lig cd Y 2p Grb2 2SH2 EGFR 1back lig cd Y

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

EGFR back lig cd 1o Y 2p Grb2 2SH2 EGFR back lig cd 1o Y

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

EGFR 1back lig cd Y 2p Grb2 2SH2 EGFR 1back lig cd Y 3p Grb2 3SH2

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 1o Y 2p Grb2 2SH2 EGFR back lig cd 1o Y 3p Grb2 3SH2

Reaction Rules

EGF binding to EGFR not crosslinked via the ectodomain.

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

EGF 1 ⬆⬇rec EGFR back 1 ⬆⬇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 2 ⬆⬇rec EGFR 1back 2 ⬆⬇lig cd c o Y u p EGFR 1back 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 3 ⬆⬇rec EGF 1rec EGFR 2back 1lig cd c o Y u p EGFR 2back 3 ⬆⬇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 1 ⬆⬇back lig cd c o Y u p EGFR 1 ⬆⬇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 2 ⬆⬇back lig cd c o Y u p EGF 1rec EGFR 2 ⬆⬇back 1lig 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 1rec EGFR 3 ⬆⬇back 1lig cd c o Y u p EGF 2rec EGFR 3 ⬆⬇back 2lig 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 1 ⬆⬇back lig cd 4o Y u p EGFR 1 ⬆⬇back lig cd 2o Y u p EGFR 3back lig cd 2o Y u p EGFR 3back lig cd 4o 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 1 ⬆⬇back lig cd 4o Y u p EGFR 1 ⬆⬇back lig cd 2o Y u p EGFR 3back lig cd 2o Y u p EGFR 3back lig cd 4o 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 1 ⬆⬇back lig cd 4o Y u p EGFR 1 ⬆⬇back lig cd 2o Y u p EGFR 3back lig cd 2o Y u p EGFR 3back lig cd 4o 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 1 ⬆⬇o Y u p EGFR back lig cd 1 ⬆⬇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 1back lig cd 4 ⬆⬇o Y u p EGFR 1back lig cd 3o Y u p EGFR 2back lig cd 3o Y u p EGFR 2back lig cd 4 ⬆⬇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 1o Y u p EGFR back lig cd 1o 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 1 ⬆⬇SH2 EGFR back lig cd c o Y 1 ⬆⬇p