##level 1 #molecules EGFR{0,EGF}{0,p,Shc,ShcP,Grb2,Sos,SosP} EGFR2{0,EGF}{0,p,Shc,ShcP,Grb2,Sos,SosP}{0,EGF}{0,p,Shc,ShcP,Grb2,Sos,SosP} IR{0,I}{0,I}{0,p,Shc,ShcP,Grb2,Sos,SosP} EGFRb{0,EGF}{0,p,Grb2,Sos,SosP} EGFRb2{0,EGF}{0,p,Grb2,Sos,SosP}{0,EGF}{0,p,Grb2,Sos,SosP} IRb{0,I}{0,I}{0,p,IRS,IRSP,Grb2,Sos,SosP} Ins EGF IRS{0,p,Grb2,Sos,SosP} Shc{0,p,Grb2,Sos,SosP} Grb2{0,Sos,SosP} Sos{0,p} #end molecules #initial conditions EGFR[0,0]=100 IR[0,0,0]=100 #end initial conditions #parameters #end parameters #algebraic relations ERKPP=100 #end algebraic relations #clamped concentrations EGF=100 Ins=100 #end clamped concentrations #reactions ## insuline / Shc binding IR[0,0,X]+Ins<->IR[I,0,X] k1 k1d IR[0,0,X]+Ins<->IR[0,I,X] k1 k1d IR[I,0,X]+Ins<->IR[I,I,X] k2 k2d IR[0,I,X]+Ins<->IR[I,I,X] k2 k2d IR[0,0,0]<->IR[0,0,p] k3 k3d IR[I,0,0]<->IR[I,0,p] k4 k4d IR[0,I,0]<->IR[0,I,p] k4 k4d IR[I,I,0]<->IR[I,I,p] k5 k5d IR[X,X,p]+Shc[0]<->IR[X,X,Shc] k6 k6d IR[X,X,p]+Shc[p]<->IR[X,X,ShcP] k6 k6d IR[X,X,p]+Shc[Grb2]<->IR[X,X,Grb2] k6 k6d IR[X,X,p]+Shc[Sos]<->IR[X,X,Sos] k6 k6d IR[X,X,p]+Shc[SosP]<->IR[X,X,SosP] k6 k6d IR[X,X,Shc]<->IR[X,X,ShcP] k7 k7d IR[X,X,ShcP]+Grb2[0]<->IR[X,X,Grb2] k8 k8d IR[X,X,ShcP]+Grb2[Sos]<->IR[X,X,Sos] k8 k8d IR[X,X,ShcP]+Grb2[SosP]<->IR[X,X,SosP] k8 k8d IR[X,X,Grb2]+Sos[0]<->IR[X,X,Sos] k9 k9d IR[X,X,Grb2]+Sos[p]<->IR[X,X,SosP] k10 k10d IR[X,X,Sos]<->IR[X,X,SosP] k11*ERKPP k11d ## insuline / IRS binding IRb[0,0,X]+Ins<->IRb[I,0,X] k1 k1d IRb[0,0,X]+Ins<->IRb[0,I,X] k1 k1d IRb[I,0,X]+Ins<->IRb[I,I,X] k2 k2d IRb[0,I,X]+Ins<->IRb[I,I,X] k2 k2d IRb[0,0,0]<->IRb[0,0,p] k12 k12d IRb[I,0,0]<->IRb[I,0,p] k13 k13d IRb[0,I,0]<->IRb[0,I,p] k13 k13d IRb[I,I,0]<->IRb[I,I,p] k14 k14d IRb[X,X,p]+IRS[0]<->IRb[X,X,IRS] k15 k15d IRb[X,X,p]+IRS[p]<->IRb[X,X,IRSP] k15 k15d IRb[X,X,p]+IRS[Grb2]<->IRb[X,X,Grb2] k15 k15d IRb[X,X,p]+IRS[Sos]<->IRb[X,X,Sos] k15 k15d IRb[X,X,p]+IRS[SosP]<->IRb[X,X,SosP] k15 k15d IRb[X,X,IRS]<->IRb[X,X,IRSP] k16 k16d IRb[X,X,IRSP]+Grb2[0]<->IRb[X,X,Grb2] k17 k17d IRb[X,X,IRSP]+Grb2[Sos]<->IRb[X,X,Sos] k17 k17d IRb[X,X,IRSP]+Grb2[SosP]<->IRb[X,X,SosP] k17 k17d IRb[X,X,Grb2]+Sos[0]<->IRb[X,X,Sos] k9 k9d IRb[X,X,Grb2]+Sos[p]<->IRb[X,X,SosP] k10 k10d IRb[X,X,Sos]<->IRb[X,X,SosP] k11*ERKPP k11d ## EGFR / Shc binding / monomers EGFR[0,X]+EGF<->EGFR[EGF,X] k21 k21d EGFR[X,0]<->EGFR[X,p] k22 k22d EGFR[X,p]+Shc[0]<->EGFR[X,Shc] k23 k23d EGFR[X,p]+Shc[p]<->EGFR[X,ShcP] k23 k23d EGFR[X,p]+Shc[Grb2]<->EGFR[X,Grb2] k23 k23d EGFR[X,p]+Shc[Sos]<->EGFR[X,Sos] k23 k23d EGFR[X,p]+Shc[SosP]<->EGFR[X,SosP] k23 k23d EGFR[X,Shc]<->EGFR[X,ShcP] k24 k24d EGFR[X,ShcP]+Grb2[0]<->EGFR[X,Grb2] k8 k8d EGFR[X,ShcP]+Grb2[Sos]<->EGFR[X,Sos] k8 k8d EGFR[X,ShcP]+Grb2[SosP]<->EGFR[X,SosP] k8 k8d EGFR[X,Grb2]+Sos[0]<->EGFR[X,Sos] k9 k9d EGFR[X,Grb2]+Sos[p]<->EGFR[X,SosP] k10 k10d EGFR[X,Sos]<->EGFR[X,SosP] k11*ERKPP k11d ## EGFR / Grb2 binding / monomers EGFRb[0,X]+EGF<->EGFRb[EGF,X] k21 k21d EGFRb[X,0]<->EGFRb[X,p] k25 k25d EGFRb[X,p]+Grb2[0]<->EGFRb[X,Grb2] k26 k26d EGFRb[X,p]+Grb2[Sos]<->EGFRb[X,Sos] k26 k26d EGFRb[X,p]+Grb2[SosP]<->EGFRb[X,SosP] k26 k26d EGFRb[X,Grb2]+Sos[0]<->EGFRb[X,Sos] k9 k9d EGFRb[X,Grb2]+Sos[p]<->EGFRb[X,SosP] k10 k10d EGFRb[X,Sos]<->EGFRb[X,SosP] k11*ERKPP k11d ## EGFR / Dimerization EGFR[EGF,X]+EGFR[0,X]<->EGFR2[EGF,X,0,X] k27 k27d EGFR[0,X]+EGFR[EGF,X]<->EGFR2[0,X,EGF,X] k27 k27d EGFR[0,X]+EGFR[0,X]<->EGFR2[0,X,0,X] k28 k28d EGFR[EGF,X]+EGFR[EGF,X]<->EGFR2[EGF,X,EGF,X] k29 k29d EGFRb[EGF,X]+EGFRb[0,X]<->EGFRb2[EGF,X,0,X] k27 k27d EGFRb[0,X]+EGFRb[EGF,X]<->EGFRb2[0,X,EGF,X] k27 k27d EGFRb[0,X]+EGFRb[0,X]<->EGFRb2[0,X,0,X] k28 k28d EGFRb[EGF,X]+EGFRb[EGF,X]<->EGFRb2[EGF,X,EGF,X] k29 k29d ## EGFR / Shc binding / dimers EGFR2[0,X,X,X]+EGF<->EGFR2[EGF,X,X,X] k30 k30d EGFR2[X,X,0,X]+EGF<->EGFR2[X,X,EGF,X] k30 k30d EGFR2[X,0,X,X]<->EGFR2[X,p,X,X] k31 k31d EGFR2[X,X,X,0]<->EGFR2[X,X,X,p] k31 k31d EGFR2[X,p,X,X]+Shc[0]<->EGFR2[X,Shc,X,X] k23 k23d EGFR2[X,p,X,X]+Shc[p]<->EGFR2[X,ShcP,X,X] k23 k23d EGFR2[X,p,X,X]+Shc[Grb2]<->EGFR2[X,Grb2,X,X] k23 k23d EGFR2[X,p,X,X]+Shc[Sos]<->EGFR2[X,Sos,X,X] k23 k23d EGFR2[X,p,X,X]+Shc[SosP]<->EGFR2[X,SosP,X,X] k23 k23d EGFR2[X,X,X,p]+Shc[0]<->EGFR2[X,X,X,Shc] k23 k23d EGFR2[X,X,X,p]+Shc[p]<->EGFR2[X,X,X,ShcP] k23 k23d EGFR2[X,X,X,p]+Shc[Grb2]<->EGFR2[X,X,X,Grb2] k23 k23d EGFR2[X,X,X,p]+Shc[Sos]<->EGFR2[X,X,X,Sos] k23 k23d EGFR2[X,X,X,p]+Shc[SosP]<->EGFR2[X,X,X,SosP] k23 k23d EGFR2[X,Shc,X,X]<->EGFR2[X,ShcP,X,X] k32 k32d EGFR2[X,ShcP,X,X]+Grb2[0]<->EGFR2[X,Grb2,X,X] k8 k8d EGFR2[X,ShcP,X,X]+Grb2[Sos]<->EGFR2[X,Sos,X,X] k8 k8d EGFR2[X,ShcP,X,X]+Grb2[SosP]<->EGFR2[X,SosP,X,X] k8 k8d EGFR2[X,Grb2,X,X]+Sos[0]<->EGFR2[X,Sos,X,X] k9 k9d EGFR2[X,Grb2,X,X]+Sos[p]<->EGFR2[X,SosP,X,X] k10 k10d EGFR2[X,Sos,X,X]<->EGFR2[X,SosP,X,X] k11*ERKPP k11d EGFR2[X,X,X,Shc]<->EGFR2[X,X,X,ShcP] k32 k32d EGFR2[X,X,X,ShcP]+Grb2[0]<->EGFR2[X,X,X,Grb2] k8 k8d EGFR2[X,X,X,ShcP]+Grb2[Sos]<->EGFR2[X,X,X,Sos] k8 k8d EGFR2[X,X,X,ShcP]+Grb2[SosP]<->EGFR2[X,X,X,SosP] k8 k8d EGFR2[X,X,X,Grb2]+Sos[0]<->EGFR2[X,X,X,Sos] k9 k9d EGFR2[X,X,X,Grb2]+Sos[p]<->EGFR2[X,X,X,SosP] k10 k10d EGFR2[X,X,X,Sos]<->EGFR2[X,X,X,SosP] k11*ERKPP k11d ## EGFR / Grb2 binding / dimers EGFRb2[0,X,X,X]+EGF<->EGFRb2[EGF,X,X,X] k30 k30d EGFRb2[X,0,X,X]<->EGFRb2[X,p,X,X] k33 k33d EGFRb2[X,p,X,X]+Grb2[0]<->EGFRb2[X,Grb2,X,X] k34 k34d EGFRb2[X,p,X,X]+Grb2[Sos]<->EGFRb2[X,Sos,X,X] k34 k34d EGFRb2[X,p,X,X]+Grb2[SosP]<->EGFRb2[X,SosP,X,X] k34 k34d EGFRb2[X,Grb2,X,X]+Sos[0]<->EGFRb2[X,Sos,X,X] k9 k9d EGFRb2[X,Grb2,X,X]+Sos[p]<->EGFRb2[X,SosP,X,X] k10 k10d EGFRb2[X,Sos,X,X]<->EGFRb2[X,SosP,X,X] k11*ERKPP k11d EGFRb2[X,X,0,X]+EGF<->EGFRb2[X,X,EGF,X] k30 k30d EGFRb2[X,X,X,0]<->EGFRb2[X,X,X,p] k33 k33d EGFRb2[X,X,X,p]+Grb2[0]<->EGFRb2[X,X,X,Grb2] k34 k34d EGFRb2[X,X,X,p]+Grb2[Sos]<->EGFRb2[X,X,X,Sos] k34 k34d EGFRb2[X,X,X,p]+Grb2[SosP]<->EGFRb2[X,X,X,SosP] k34 k34d EGFRb2[X,X,X,Grb2]+Sos[0]<->EGFRb2[X,X,X,Sos] k9 k9d EGFRb2[X,X,X,Grb2]+Sos[p]<->EGFRb2[X,X,X,SosP] k10 k10d EGFRb2[X,X,X,Sos]<->EGFRb2[X,X,X,SosP] k11*ERKPP k11d Shc[0]<->Shc[p] k18 k18d Shc[p]+Grb2[0]<->Shc[Grb2] k8 k8d Shc[p]+Grb2[Sos]<->Shc[Sos] k8 k8d Shc[p]+Grb2[SosP]<->Shc[SosP] k8 k8d Grb2[0]+Sos[0]<->Grb2[Sos] k9 k9d Grb2[0]+Sos[p]<->Grb2[SosP] k10 k10d Shc[Grb2]+Sos[0]<->Shc[Sos] k9 k9d Shc[Grb2]+Sos[p]<->Shc[SosP] k10 k10d IRS[Grb2]+Sos[0]<->IRS[Sos] k9 k9d IRS[Grb2]+Sos[p]<->IRS[SosP] k10 k10d Sos[0]<->Sos[p] k19*ERKPP k19d Grb2[Sos]<->Grb2[SosP] k11*ERKPP k11d Shc[Sos]<->Shc[SosP] k11*ERKPP k11d IRS[0]<->IRS[p] k20 k20d IRS[p]+Grb2[0]<->IRS[Grb2] k17 k17d IRS[p]+Grb2[Sos]<->IRS[Sos] k17 k17d IRS[p]+Grb2[SosP]<->IRS[SosP] k17 k17d IRS[Sos]<->IRS[SosP] k11*ERKPP k11d #end reactions #output IR[X,X,Shc]+IR[X,X,ShcP]+IR[X,X,Grb2]+IR[X,X,Sos]+IR[X,X,SosP] IR[X,X,ShcP]+IR[X,X,Grb2]+IR[X,X,Sos]+IR[X,X,SosP] IR[X,X,Grb2]+IR[X,X,Sos]+IR[X,X,SosP] IR[X,X,Sos]+IR[X,X,SosP] IR[X,X,SosP] #end output