begin name faratian1 end name begin reactions R1 {1.0}E3 + {1.0}HRG = {1.0}E3H R10 {1.0}ShcP = {1.0}Shc R11 {1.0}RasGDP = {1.0}RasGTP R12 {1.0}RasGTP = {1.0}RasGDP R13 {1.0}Raf = {1.0}Rafa R14 {1.0}Rafa = {1.0}Raf R15 {1.0}MEK = {1.0}MEKP R161 {1.0}MEKP + {1.0}PP2A = {1.0}MEKPPP2A R162 {1.0}MEKPPP2A = {1.0}MEKPP2A R163 {1.0}MEKPP2A = {1.0}MEK + {1.0}PP2A R171 {1.0}MEKP = {1.0}MEKPP R181 {1.0}MEKPP + {1.0}PP2A = {1.0}MEKPPPP2A R182 {1.0}MEKPPPP2A = {1.0}MEKPPP2A R183 {1.0}MEKPPP2A = {1.0}MEKP + {1.0}PP2A R19 {1.0}ERK = {1.0}ERKP R2 {1.0}E2 + {1.0}E3H = {1.0}E23H R20 {1.0}ERKP = {1.0}ERK R21 {1.0}ERKP = {1.0}ERKPP R22 {1.0}ERKPP = {1.0}ERKP R23 {1.0}E23HP + {1.0}PI3K = {1.0}E23HPPI3K R24 {1.0}E23HPPI3K = {1.0}E23HPPI3Ka R25 {1.0}E23HPPI3Ka = {1.0}E23HP + {1.0}PI3Ka R26 {1.0}PI3Ka = {1.0}PI3K R271 {1.0}PI2 + {1.0}PI3Ka = {1.0}PI3KaPI R281 {1.0}PIP3 + {1.0}PTEN = {1.0}PTENPIP3 R282 {1.0}PTENPIP3 = {1.0}PTENPI R283 {1.0}PTENPI = {1.0}PI2 + {1.0}PTEN R284 {1.0}PTEN = {1.0}PTENP R285 {1.0}PTEN + {1.0}PTENP = {1.0}PTENPPTEN R286 {1.0}PTENPPTEN = {1.0}PTENPTEN R287 {1.0}PTENPTEN = {2.0}PTEN R29 {1.0}PIP3 + {1.0}Akt = {1.0}AktPIP3 R3 {1.0}E23H = {1.0}E23HP R30 {1.0}AktPIP3 = {1.0}AktPIP R311 {1.0}AktPIP + {1.0}PP2A = {1.0}AktPIPPP2A R312 {1.0}AktPIPPP2A = {1.0}AktPIP3PP2A R313 {1.0}AktPIP3PP2A = {1.0}AktPIP3 + {1.0}PP2A R32 {1.0}AktPIP = {1.0}AktPIPP R331 {1.0}AktPIPP + {1.0}PP2A = {1.0}AktPIPPPP2A R332 {1.0}AktPIPPPP2A = {1.0}AktPIPPP2A R333 {1.0}AktPIPPP2A = {1.0}AktPIP + {1.0}PP2A R34 {1.0}E23HP = {1.0}$EXTERNAL R35 {1.0}E2 + {1.0}Per = {1.0}E2Per R36 {1.0}E2Per = {1.0}E2Per R37 {1.0}E3H = {1.0}E3HC R38 {1.0}E2 + {1.0}E3HC = {1.0}E23H R39 {1.0}E23H = {1.0}E23HC R4 {1.0}E23HP = {1.0}E23H R40 {1.0}E23HC = {1.0}E23HP R41 {1.0}PI3KaPI = {1.0}PI3KaPIP3 R42 {1.0}PI3KaPIP3 = {1.0}PI3Ka + {1.0}PIP3 R43 {1.0}PTEN = {1.0}PTENbpV R44 {1.0}PI3K = {1.0}PI3KLY R5 {1.0}E23HP + {1.0}Shc = {1.0}E23HPShc R6 {1.0}E23HPShc = {1.0}E23HPShcP R7 {1.0}E23HPShcP + {1.0}GS = {1.0}E23HPShGS R8 {1.0}E23HPShGS = {1.0}E23HP + {1.0}ShGS R9 {1.0}ShGS = {1.0}GS + {1.0}ShcP end reactions begin rate equations R1 = k1*(-(Kd1*E3H[t]) + E3[t]*HRG[t]) R10 = (V10*ShcP[t])/(K10 + ShcP[t]) R11 = (k11*RasGDP[t]*ShGS[t])/(K11 + RasGDP[t]) R12 = (V12*RasGTP[t])/(K12 + RasGTP[t]) R13 = (k13*Raf[t]*RasGTP[t])/(K13 + Raf[t]) R14 = (k14*(Eraf + AktPIPP[t])*Rafa[t])/(K14 + Rafa[t]) R15 = (k15*MEK[t]*Rafa[t])/(K15 + MEK[t]) R161 = k16*MEKP[t]*PP2A[t] R162 = k16kat*MEKPPP2A[t] R163 = k18*MEKPP2A[t] R171 = (k15*MEKP[t]*Rafa[t])/(K15 + MEKP[t]) R181 = k16*(-(Kd16*MEKPPPP2A[t]) + MEKPP[t]*PP2A[t]) R182 = k16kat*MEKPPPP2A[t] R183 = k22*MEKPPP2A[t] R19 = (k23*ERK[t]*MEKPP[t])/(K23 + ERK[t]) R2 = k2*(-(Kd2*E23H[t]) + E2[t]*E3H[t]) R20 = (V24*ERKP[t])/(K24 + ERKP[t]) R21 = (k23*ERKP[t]*MEKPP[t])/(K23 + ERKP[t]) R22 = (V24*ERKPP[t])/(K24 + ERKPP[t]) R23 = k27*(-(Kd27*E23HPPI3K[t]) + E23HP[t]*PI3K[t]) R24 = k28*(E23HPPI3K[t] - k28*E23HPPI3Ka[t]) R25 = k29*E23HPPI3Ka[t] - k29*E23HP[t]*PI3Ka[t] R26 = V30*PI3Ka[t] R271 = k31*(PI2[t]*PI3Ka[t] - Kd31*PI3KaPI[t]) R281 = k32*(PIP3[t]*PTEN[t] - Kd32*PTENPIP3[t]) R282 = k33*PTENPIP3[t] R283 = k34*PTENPI[t] R284 = (V35*PTEN[t])/(K35 + PTEN[t]) R285 = k36*(PTEN[t]*PTENP[t] - Kd36*PTENPPTEN[t]) R286 = k37*PTENPPTEN[t] R287 = k38*PTENPTEN[t] R29 = k39*(-(Kd39*AktPIP3[t]) + Akt[t]*PIP3[t]) R3 = k3*(E23H[t] - Kd3*E23HP[t]) R30 = (V40*AktPIP3[t])/(K40 + AktPIP3[t]) R311 = k41*AktPIP[t]*PP2A[t] R312 = k42*AktPIPPP2A[t] R313 = k43*AktPIP3PP2A[t] R32 = (V40*AktPIP[t])/(K40 + AktPIP[t]) R331 = k41*(-(Kd41*AktPIPPPP2A[t]) + AktPIPP[t]*PP2A[t]) R332 = k42*AktPIPPPP2A[t] R333 = k47*AktPIPPP2A[t] R34 = k48*E23HP[t] R35 = k49*(-(Kd49*E2Per[t]) + E2[t]*Per[t]) R36 = -(k50*E2Per[t]) + k50*E2Per[t] R37 = k51*E3H[t] R38 = k2*(-(Kd2*E23H[t]) + E2[t]*E3HC[t]) R39 = k53*E23H[t] R4 = (V4*E23HP[t])/(K4 + E23HP[t]) R40 = k3*(-(Kd3*E23HP[t]) + E23HC[t]) R41 = k55*PI3KaPI[t] R42 = k56*PI3KaPIP3[t] R43 = k57*(bpV*PTEN[t] - Kd57*PTENbpV[t]) R44 = k58*(LY*PI3K[t] - Kd58*PI3KLY[t]) R5 = k5*(-(Kd5*E23HPShc[t]) + E23HP[t]*Shc[t]) R6 = k6*E23HPShc[t] - k6*E23HPShcP[t] R7 = k7*(-(Kd7*E23HPShGS[t]) + E23HPShcP[t]*GS[t]) R8 = k8*(E23HPShGS[t] - Kd8*E23HP[t]*ShGS[t]) R9 = k9*(-(k9*GS[t]*ShcP[t]) + ShGS[t]) end rate equations begin parameters Akt0 = 10.0 E30 = 0.0 Eraf = 7.0 K10 = 340.0 K11 = 0.18 K12 = 0.1 K13 = 11.7 K14 = 50.0 K15 = 1.0 K23 = 10.0 K24 = 10.0 K35 = 2.0 K4 = 50.0 K40 = 0.1 Kd31 = 100.0 Kd1 = 600.0 Kd16 = 1.0 Kd2 = 10.0 Kd27 = 1.0 Kd3 = 0.1 Kd32 = 0.01 Kd36 = 2.2 Kd39 = 20.0 Kd41 = 0.1 Kd49 = 20000.0 Kd5 = 1.0 Kd57 = 10.0 Kd58 = 80.0 Kd7 = 9.0 Kd8 = 0.1 LY = 0.0 PI0 = 70.0 PI3KCY = 0.0 Pool10 = 10.0 Pool11 = 100.0 Pool12 = 120.0 Pool13 = 100.0 Pool14 = 100.0 Pool1 = 2900.0 Pool2 = -2920.0 Pool3 = 200.0 Pool4 = 50.0 Pool5 = 300.0 Pool6 = 0.0 Pool7 = 10.0 Pool8 = 100.0 Pool9 = 10.0 V10 = 0.0154 V12 = 3.0 V24 = 1.8 V30 = 900.0 V35 = 150.0 V4 = 10.0 V40 = 15000.0 bpV = 0.0 k1 = 0.005 k11 = 6.0 k13 = 1.0 k14 = 0.6 k15 = 2.1 k16 = 0.06 k16kat = 0.6 k18 = 0.6 k2 = 10.0 k22 = 0.06 k23 = 1.2 k27 = 3.0 k28 = 300.0 k29 = 13520.0 k3 = 1.0 k31 = 0.03 k32 = 8000.0 k33 = 15.0 k34 = 3.6 k36 = 1.0 k37 = 150.0 k38 = 150.0 k39 = 15000.0 k41 = 3.0 k42 = 45.0 k43 = 30.0 k47 = 0.3 k48 = 0.001 k49 = 0.003 k5 = 0.06 k50 = 0.6 k51 = 0.01 k53 = 0.01 k55 = 30.0 k56 = 30.0 k57 = 100.0 k58 = 100.0 k6 = 12.0 k7 = 36.0 k8 = 12.0 k9 = 35.0 k28 = 0.0 k29 = 0.0 k50 = 0.012 k6 = 3.0 k9 = 0.0 mu = 0.0 pAktmax = 91.0 scal = 1.0 scall = 0.6 scalll = 30.0 sens = 0.0 tE3Pmax = 65.0 tERKPmax = 10.0 Default = 1.0 end parameters begin initial conditions Akt[0] = Akti AktPIP3[0] = AktPIP3i AktPIP3PP2A[0] = AktPIP3PP2Ai AktPIP[0] = AktPIPi AktPIPP[0] = AktPIPPi AktPIPPPP2A[0] = AktPIPPPP2Ai AktPIPPP2A[0] = AktPIPPP2Ai E2[0] = E2i E23H[0] = E23Hi E23HP[0] = E23HPi E23HPPI3K[0] = E23HPPI3Ki E23HPPI3Ka[0] = E23HPPI3Kai E23HPShGS[0] = E23HPShGSi E23HPShc[0] = E23HPShci E23HPShcP[0] = E23HPShcPi E23HC[0] = E23HCi E2Per[0] = E2Peri E2Per[0] = E2Peri E3[0] = E3i E3H[0] = E3Hi E3HC[0] = E3HCi ERK[0] = ERKi ERKP[0] = ERKPi ERKPP[0] = ERKPPi GS[0] = GSi HRG[0] = HRGi MEK[0] = MEKi MEKP[0] = MEKPi MEKPP[0] = MEKPPi MEKPPPP2A[0] = MEKPPPP2Ai MEKPPP2A[0] = MEKPPP2Ai MEKPP2A[0] = MEKPP2Ai PI2[0] = PI2i PI3K[0] = PI3Ki PI3KLY[0] = PI3KLYi PI3Ka[0] = PI3Kai PI3KaPI[0] = PI3KaPIi PI3KaPIP3[0] = PI3KaPIP3i PIP3[0] = PIP3i PP2A[0] = PP2Ai PTEN[0] = PTENi PTENP[0] = PTENPi PTENPPTEN[0] = PTENPPTENi PTENPI[0] = PTENPIi PTENPIP3[0] = PTENPIP3i PTENPTEN[0] = PTENPTENi PTENbpV[0] = PTENbpVi Per[0] = Peri Raf[0] = Rafi Rafa[0] = Rafai RasGDP[0] = RasGDPi RasGTP[0] = RasGTPi ShGS[0] = ShGSi Shc[0] = Shci ShcP[0] = ShcPi end initial conditions begin initial values Akti = 100.0 AktPIP3i = 0.0 AktPIP3PP2Ai = 0.0 AktPIPi = 0.0 AktPIPPi = 0.0 AktPIPPPP2Ai = 0.0 AktPIPPP2Ai = 0.0 E2i = 100.0 E23Hi = 0.0 E23HPi = 0.0 E23HPPI3Ki = 0.0 E23HPPI3Kai = 0.0 E23HPShGSi = 0.0 E23HPShci = 0.0 E23HPShcPi = 0.0 E23HCi = 0.0 E2Peri = 0.0 E2Peri = 0.0 E3i = 80.0 E3Hi = 0.0 E3HCi = 0.0 ERKi = 10.0 ERKPi = 0.0 ERKPPi = 0.0 GSi = 100.0 HRGi = 3000.0 MEKi = 10.0 MEKPi = 0.0 MEKPPi = 0.0 MEKPPPP2Ai = 0.0 MEKPPP2Ai = 0.0 MEKPP2Ai = 0.0 PI2i = 300.0 PI3Ki = 200.0 PI3KLYi = 0.0 PI3Kai = 0.0 PI3KaPIi = 0.0 PI3KaPIP3i = 0.0 PIP3i = 8.05772e-12 PP2Ai = 10.0 PTENi = 42.7798 PTENPi = 3.39885 PTENPPTENi = 0.955337 PTENPIi = 5.02914e-08 PTENPIP3i = 3.14554e-08 PTENPTENi = 0.955337 PTENbpVi = 0.0 Peri = 0.0 Rafi = 100.0 Rafai = 0.0 RasGDPi = 120.0 RasGTPi = 0.0 ShGSi = 0.0 Shci = 100.0 ShcPi = 0.0 end initial values begin assignment rules tERKP := (ERKP[t] + ERKPP[t])/tERKPmax pAkt := (AktPIP[t] + AktPIPP[t] + AktPIPPPP2A[t] + AktPIPPP2A[t])/pAktmax tPTENP := 0.13157894736842105*PTENP[t] tPTEN := PTEN[t] + PTENP[t] + PTENPPTEN[t] + PTENPI[t] + PTENPIP3[t] + PTENPTEN[t] tE3P := (E23HP[t] + E23HPPI3K[t] + E23HPPI3Ka[t] + E23HPShc[t] + E23HPShcP[t] + E23HPShGS[t])/tE3Pmax end assignment rules begin function definitions end function definitions begin events end events begin process annotations end process annotations begin species annotations Shc http://identifiers.org/uniprot/P29353 end species annotations begin units end units