#fujita

FIX: EGF

#reactions
re1:
 {1.0}EGFR + {1.0}EGF = {1.0}EGF_EGFR
  function_1(EGF, EGFR, kf_EGFEGFR, kphos_EGFR_mutant)
re12:
 {1.0}pMEKcyt + {1.0}ERKcyt = {1.0}pMEK_ERK_cyt
  c1 * function_8(ERKcyt, c1, kb_MEKERK, kf_MEKERK, pMEK_ERK_cyt, pMEKcyt)
re15:
 {1.0}pTpYERK_cyt = {1.0}pTpYERK_nuc
  function_9(c2, kexport_pTpYERK, kimport_pTpYERK, pTpYERK_cyt, pTpYERK_nuc)
re16:
 {1.0}ERKcyt = {1.0}ERKnuc
  function_10(ERKcyt, ERKnuc, c2, kexport_ERK, kimport_ERK)
re2:
 {1.0}EGF_EGFR = {1.0}degra_EGF_pEGFR
  c1 * function_2(EGF_EGFR, c1, degra_EGF_pEGFR, kb_degra, kf_degra)
re22:
 {1.0}pMEKcyt = {1.0}MEKcyt
  c1 * function_11(c1, kf_dpMEK, pMEKcyt)
re27:
 {1.0}RasEffector + {1.0}Ras_GTP = {1.0}RassEffector
  c1 * function_12(RasEffector, RassEffector, Ras_GTP, c1, kb_RasEffector, kf_RasEffector)
re28:
 {1.0}Sos1_2 = {1.0}pSos
  c1 * function_13(Km_pERKcyt, Sos1_2, c1, kb_pSos, kcat_pERKcyt, kf_pSos, pSos, pTpYERK_cyt)
re3:
 {1.0}Sos1_2 + {1.0}EGF_EGFR = {1.0}EGFR_Sos
  c1 * function_3(EGFR_Sos, EGFR_inhibitor, EGF_EGFR, Sos1_2, c1, kb_Sos, kf_Sos)
re30:
 {1.0}pSos = {1.0}ppSos
  c1 * function_14(Km_pERKcyt, c1, kb_pSos, kcat_pERKcyt, kfb_ppSos, pSos, pTpYERK_cyt, ppSos)
re31:
 {1.0}ppSos = {1.0}pppSos
  c1 * function_15(Km_pERKcyt, c1, kb_pSos, kcat_pERKcyt, kfb_pppSos, pTpYERK_cyt, ppSos, pppSos)
re32:
 {1.0}pppSos = {1.0}ppppSos
  c1 * function_16(Km_pERKcyt, c1, kb_pSos, kcat_pERKcyt, kfb_ppppSos, pTpYERK_cyt, pppSos, ppppSos)
re4:
 {1.0}Ras_GDP = {1.0}Ras_GTP
  c1 * function_4(EGFR_Sos, RasGEF, Ras_GDP, c1, kf_RasGEF, kf_Sos_Ras)
re42:
 {1.0}pMEK_ERK_cyt = {1.0}pMEK_pYERK
  c1 * function_17(MEK_inhibitor, c1, kphos_np_pY, pMEK_ERK_cyt)
re43:
 {1.0}pMEK_pYERK = {1.0}pMEKcyt + {1.0}pTpYERK_cyt
  c1 * function_18(MEK_inhibitor, c1, kphos_pY_pTpY_MEKERK, pMEK_pYERK)
re44:
 {1.0}pTpYERK_cyt = {1.0}pTERK_cyt
  c1 * function_19(c1, kdphos_pTpY_pT_cyt, pTpYERK_cyt)
re45:
 {1.0}pTpYERK_cyt = {1.0}pYERK_cyt
  c1 * function_20(c1, kdphos_pTpY_pY_cyt, pTpYERK_cyt)
re46:
 {1.0}pYERK_cyt = {1.0}ERKcyt
  c1 * function_21(c1, kdphos_pY_np_cyt, pYERK_cyt)
re47:
 {1.0}pTERK_cyt = {1.0}ERKcyt
  c1 * function_22(c1, kdphos_pT_np_cyt, pTERK_cyt)
re48:
 {1.0}pYERK_cyt = {1.0}pTpYERK_cyt
  c1 * function_23(MEK_inhibitor, c1, kphos_pY_pTpY, pMEKcyt, pYERK_cyt)
re49:
 {1.0}pTERK_cyt = {1.0}pTpYERK_cyt
  c1 * function_24(MEK_inhibitor, c1, kphos_pT_pTpY, pMEKcyt, pTERK_cyt)
re5:
 {1.0}Ras_GTP = {1.0}Ras_GDP
  c1 * function_5(RasGAP, Ras_GTP, c1, kf_RasGAP, mutated_Ras)
re50:
 {1.0}pYERK_cyt = {1.0}pYERK_nuc
  function_25(c2, kexport_pYERK, kimport_pYERK, pYERK_cyt, pYERK_nuc)
re51:
 {1.0}pTERK_cyt = {1.0}pTERK_nuc
  function_26(c2, kexport_pTERK, kimport_pTERK, pTERK_cyt, pTERK_nuc)
re52:
 {1.0}pTpYERK_nuc = {1.0}pYERK_nuc
  c2 * kdphos_pTpY_pY_nuc * pTpYERK_nuc
re53:
 {1.0}pTpYERK_nuc = {1.0}pTERK_nuc
  c2 * kdphos_pTpY_pT_nuc * pTpYERK_nuc
re54:
 {1.0}pYERK_nuc = {1.0}ERKnuc
  c2 * kdphos_pY_np_nuc * pYERK_nuc
re55:
 {1.0}pTERK_nuc = {1.0}ERKnuc
  c2 * kdphos_pT_np_nuc * pTERK_nuc
re56:
 {1.0}MEKcyt = {1.0}pMEKcyt
  c1 * function_27(BRaf, BRaf_inhibitor, MEKcyt, Ras_Raf, Ras_Shoc2_cRaf, c1, kf_pMEK, kphos_BRafMEK)
re57:
 {1.0}Shoc2 + {1.0}Ras_GTP = {1.0}Ras_Shoc2
  c1 * function_28(Ras_GTP, Ras_Shoc2, Shoc2, c1, kb_Ras_Shoc2, kf_Ras_Shoc2)
re58:
 {1.0}cRaf + {1.0}Ras_Shoc2 = {1.0}Ras_Shoc2_cRaf
  c1 * function_29(Ras_Shoc2, Ras_Shoc2_cRaf, c1, cRaf, kb_RasRaf_Shoc2, kf_RasRaf_Shoc2)
re6:
 {1.0}cRaf + {1.0}Ras_GTP = {1.0}Ras_Raf
  c1 * function_6(Ras_GTP, Ras_Raf, c1, cRaf, kb_RasRaf, kf_RasRaf)
re62:
 {1.0}PI3K = {1.0}active_PI3K
  c1 * function_30(EGFR_inhibitor, EGF_EGFR, PI3K, Ras_GTP, active_PI3K, c1, kact_EGFRRasPI3K, kdact_PI3K, mutated_PI3K)
re63:
 {1.0}Akt = {1.0}pAkt
  c1 * function_31(Akt, PI3K_inhibitor, active_PI3K, c1, kdphos_pAkt, kphos_PI3KAkt, pAkt)
re64:
 {1.0}TSC = {1.0}pTSC
  c1 * function_32(TSC, c1, kdphos_pTSC, kphos_AktTSC, kphos_RSKTSC, pAkt, pRSK, pTSC)
re65:
 {1.0}Rheb_GTP = {1.0}Rheb_GDP
  c1 * function_33(Rheb_GDP, Rheb_GTP, TSC, c1, kact_Rheb, kdact_TSCRheb)
re66:
 {1.0}S6K = {1.0}pS6K
  c1 * function_34(Rheb_GTP, S6K, c1, kdphos_pS6K, kphos_RhebS6K, pS6K)
re67:
 {1.0}RSK = {1.0}pRSK
  c1 * function_35(RSK, c1, kdphos_pRSK, kphos_ERKRSK, pRSK, pTpYERK_cyt)
re68:
 {1.0}cRaf = {1.0}inactive_cRaf
  c1 * function_36(Rheb_GTP, c1, cRaf, inactive_cRaf, kact_RhebRaf, kdact_RhebRaf)
re69:
 {1.0}EGF_EGFR = {1.0}degra_EGF_pEGFR
  c1 * function_37(EGF_EGFR, c1, kf_degra_ERKEGFR, pTpYERK_cyt)
re70:
 {1.0}inactive_cRaf = {1.0}cRaf
  c1 * function_38(PI3K_inhibitor, active_PI3K, c1, inactive_cRaf, kact_PI3KRaf)
re9:
 {1.0}ERKcyt + {1.0}MEKcyt = {1.0}MEK_ERK_cyt
  c1 * function_7(ERKcyt, MEK_ERK_cyt, MEKcyt, c1, kb_MEKERK, kf_MEKERK)


#parameters
Km_pERKcyt = 3.0
kact_EGFRRasPI3K = 3.0
kact_PI3KRaf = 1.8
kact_Rheb = 0.0021
kact_RhebRaf = 0.04
kb_MEKERK = 0.27
kb_RafMEK = 0.065
kb_RasEffector = 0.1
kb_RasRaf = 0.0049
kb_RasRaf_Shoc2 = 0.049
kb_Ras_Shoc2 = 0.1
kb_Sos = 0.1
kb_degra = 0.001
kb_pSos = 0.0025
kcat_pERKcyt = 0.075
kdact_PI3K = 0.028
kdact_RhebRaf = 4.0
kdact_TSCRheb = 0.097
kdphos_pAkt = 0.048
kdphos_pRSK = 0.3
kdphos_pS6K = 0.001
kdphos_pTSC = 0.0088
kdphos_pT_np_cyt = 0.0068
kdphos_pT_np_nuc = 0.0058
kdphos_pTpY_pT_cyt = 0.0055
kdphos_pTpY_pT_nuc = 0.0038
kdphos_pTpY_pY_cyt = 0.004
kdphos_pTpY_pY_nuc = 0.0032
kdphos_pY_np_cyt = 0.0067
kdphos_pY_np_nuc = 0.0077
kexport_ERK = 0.013
kexport_pTERK = 0.049
kexport_pTpYERK = 0.0076
kexport_pYERK = 0.017
kf_EGFEGFR = 10.0
kf_MEKERK = 0.18
kf_RafMEK = 0.65
kf_RasEffector = 1.0
kf_RasGAP = 0.05
kf_RasGEF = 9e-05
kf_RasRaf = 0.049
kf_RasRaf_Shoc2 = 0.49
kf_Ras_Shoc2 = 1.0
kf_Sos = 0.1
kf_Sos_Ras = 1.0
kf_degra = 0.0014
kf_degra_ERKEGFR = 0.02
kf_dpMEK = 0.0096
kf_pMEK = 2.0
kf_pSos = 1.0
kfb_ppSos = 1.0
kfb_pppSos = 1.0
kfb_ppppSos = 1.0
kimport_ERK = 0.0017
kimport_pTERK = 0.0022
kimport_pTpYERK = 0.0082
kimport_pYERK = 0.0025
kphos_AktTSC = 1.2
kphos_BRafMEK = 0.01
kphos_EGFR_mutant = 0.0
kphos_ERKRSK = 0.7
kphos_PI3KAkt = 0.1
kphos_RSKTSC = 0.6
kphos_RhebS6K = 0.002
kphos_np_pY = 0.073
kphos_pT_pTpY = 0.02
kphos_pY_pTpY = 0.02
kphos_pY_pTpY_MEKERK = 0.05
EGF = 0.0
c1 = 1.0
c2 = 0.2
default = 1.0


#initial values
Akt = 1.0
BRaf = 0.0
BRaf_inhibitor = 1.0
EGFR = 0.42
EGFR_Sos = 0.0
EGFR_inhibitor = 1.0
EGF_EGFR = 0.0
ERKcyt = 0.96
ERKnuc = 0.0
MEK_ERK_cyt = 0.0
MEK_inhibitor = 1.0
MEKcyt = 1.4
PI3K = 1.0
PI3K_inhibitor = 1.0
RSK = 1.0
RasEffector = 2.0
RasGAP = 1.0
RasGEF = 1.0
Ras_GDP = 0.43
Ras_GTP = 0.0
Ras_Raf = 0.0
Ras_Shoc2 = 0.0
Ras_Shoc2_cRaf = 0.0
RassEffector = 0.0
Rheb_GDP = 1.0
Rheb_GTP = 0.0
S6K = 1.0
Shoc2 = 0.67
Sos1_2 = 0.12
TSC = 1.0
active_PI3K = 0.0
cRaf = 0.013
degra_EGF_pEGFR = 0.0
inactive_cRaf = 0.0
mutated_PI3K = 0.0
mutated_Ras = 0.0
pAkt = 0.0
pMEK_ERK_cyt = 0.0
pMEK_pYERK = 0.0
pMEKcyt = 0.0
pRSK = 0.0
pS6K = 0.0
pSos = 0.0
pTERK_cyt = 0.0
pTERK_nuc = 0.0
pTSC = 0.0
pTpYERK_cyt = 0.0
pTpYERK_nuc = 0.0
pYERK_cyt = 0.0
pYERK_nuc = 0.0
ppSos = 0.0
pppSos = 0.0
ppppSos = 0.0


#assignment rules