#adlung2



#reactions
v1:
 $pool = {1.0}pEpoR
  EpoRactivation / (1 + phos2 / Ki) * (EpoRCFUE - pEpoR * (1 + kPI3K / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) + kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1))) * (pow(Epo, nc) / (pow(ksatc, nc) + pow(Epo, nc)))
v17:
 $pool = {1.0}RpSHIP1
  kSHIP1 * (SHIP1tCFUE - RpSHIP1) * (pEpoR - RpSHIP1)
v18:
 {1.0}RpSHIP1 = $pool
  lSHIP1 * RpSHIP1
v19:
 $pool = {1.0}PIP3
  vPIP3 * PI45P2CFUE * kPI3K / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR
v2:
 $pool = {1.0}actPhosphatase
  Phosphataseactivation * (PhosphatasetCFUE - actPhosphatase) * pEpoR
v20:
 $pool = {1.0}PIP3
  vPIP3 * main * PI45P2CFUE * kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR
v21:
 {1.0}PIP3 = $pool
  kshbasal * PIP3 * (SHIP1tCFUE - RpSHIP1)
v22:
 {1.0}PIP3 = $pool
  vPI45P2 * PIP3 * PTENCFUE
v23:
 {1.0}PIP3 = $pool
  vPI34P2 * PIP3 * RpSHIP1
v24:
 {1.0}PIP3 = {1.0}PIP3PDK1
  kPDK1 * PIP3 * (PDK1tCFUE - PIP3PDK1)
v25:
 {1.0}PIP3PDK1 = {1.0}PIP3
  lPDK1 * PIP3PDK1
v26:
 {1.0}PIP3 = {1.0}PIP3Akt
  kAkt * PIP3 * (AkttCFUE - PIP3Akt - pAkt)
v27:
 {1.0}PIP3Akt = {1.0}PIP3
  lAkt * PIP3Akt
v28:
 {1.0}PIP3Akt = $pool
  vpAkt * PIP3Akt * PIP3PDK1
v29:
 $pool = {1.0}PIP3
  vpAkt * PIP3Akt * PIP3PDK1
v3:
 {1.0}actPhosphatase = $pool
  Phosphatasedeactivation * actPhosphatase
v30:
 $pool = {1.0}pAkt
  vpAkt * PIP3Akt * PIP3PDK1 / (1 + kaktinc * Aktin)
v31:
 {1.0}pAkt = $pool
  dpAkt * pAkt
v32:
 $pool = {1.0}PIP3
  vPIP3basal * PI45P2CFUE * (PI3KtCFUE - kPI3K / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR - kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR)
v33:
 $pool = {1.0}PIP3
  vPIP3basal * main * PI45P2CFUE
v34:
 $pool = {1.0}pSos
  kpes * (Sostc - pSos - RpSos) * ppErk
v35:
 {1.0}pSos = $pool
  kdpes * pSos
v36:
 $pool = {1.0}RpSos
  kSos * (Sostc - RpSos - pSos) * (pEpoR - RpSos)
v37:
 {1.0}RpSos = $pool
  lSos * RpSos
v38:
 {1.0}RpSos = {1.0}pSos
  kpes * RpSos * ppErk
v39:
 $pool = {1.0}GTPRas
  kbackRas * (RastCFUE - GTPRas - kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR)
v4:
 {1.0}pEpoR = $pool
  pEpoRdeactivation * pEpoR * actPhosphatase
v40:
 $pool = {1.0}GTPRas
  kaRas * RpSos * (RastCFUE - GTPRas - kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR)
v41:
 {1.0}GTPRas = $pool
  kdRas * GTPRas
v42:
 $pool = {1.0}pRaf
  kpRaf * (GTPRas + kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR) * (RaftCFUE - pRaf)
v43:
 {1.0}pRaf = $pool
  lpRaf * pRaf
v44:
 $pool = {1.0}pMek
  kpMek * pRaf * (MektCFUE - pMek - ppMek)
v45:
 {1.0}pMek = $pool
  lpMek * pMek
v46:
 {1.0}pMek = {1.0}ppMek
  kppMek * pRaf * pMek
v47:
 {1.0}ppMek = {1.0}pMek
  lppMek * ppMek
v48:
 $pool = {1.0}pErk
  kpErk * ppMek * (ErktCFUE - pErk - ppErk)
v49:
 {1.0}pErk = $pool
  lpErk * cDUSP3 * pErk
v5:
 $pool = {1.0}phos2
  Phosact * pow(pEpoR, n) / (pow(Ji, n) + pow(pEpoR, n))
v50:
 {1.0}pErk = {1.0}ppErk
  kppErk * ppMek * pErk / (1 + kmekinc * Mekin)
v51:
 {1.0}ppErk = {1.0}pErk
  lppErk * cDUSP3 * ppErk
v52:
 $pool = {1.0}Intperk
  ppErk
v53:
 $pool = {1.0}Intpakt
  pAkt
v54:
 $pool = {1.0}mTORa
  kvpakt * pAkt * (mTORt - mTORa - TORC1 - TORC2)
v55:
 $pool = {1.0}mTORa
  kvppErk * RSKa / (1 + kinrskc * RSKin) * (mTORt - mTORa - TORC1 - TORC2)
v56:
 {1.0}mTORa = $pool
  kdactm * mTORa
v57:
 {1.0}mTORa = {1.0}TORC1
  kst1 / (1 + kinrapac * Rapamycin) * (mTORa - TORC1 - TORC2) * (Raptorc - TORC1)
v58:
 {1.0}TORC1 = {1.0}mTORa
  kdt1 * TORC1
v59:
 {1.0}TORC1 = $pool
  kdactm * TORC1
v6:
 {1.0}phos2 = $pool
  Phosdeact * phos2
v60:
 {1.0}mTORa = {1.0}TORC2
  kst2 * (mTORa - TORC2 - TORC1) * (Rictorc - TORC2)
v61:
 {1.0}TORC2 = $pool
  kdactm * TORC2
v62:
 {1.0}TORC2 = {1.0}mTORa
  kdt2 * TORC2
v63:
 $pool = {1.0}RSKa
  karsk / (1 + kinrskc * RSKin) * (RSKtc - RSKa) * ppErk
v64:
 {1.0}RSKa = $pool
  kdrsk * RSKa
v65:
 $pool = {1.0}pS6
  kas6t * TORC1 * (S6tCFUE - pS6)
v66:
 $pool = {1.0}pS6
  kas6r * RSKa * (S6tCFUE - pS6)
v67:
 $pool = {1.0}pS6
  kbacks6 * (S6tCFUE - pS6)
v68:
 {1.0}pS6 = $pool
  kdphoss6 * pS6
v69:
 $pool = {1.0}Proliferation
  pck1correct * (pS6 / max6c) + pcoffcorrect / 60
v70:
 $pool = {1.0}IntpS6
  pS6


#parameters
Aktin = 0.0
EpoRactivation = 1.17558
Ji = 0.000187303
Ki = 0.0237162
Mekin = 0.0
Phosact = 0.0125808
Phosdeact = 1e-05
Phosphataseactivation = 77.7544
Phosphatasedeactivation = 1e-05
RSKin = 0.0
Rapamycin = 0.0
Sostc = 9.74717e-05
cDUSP3 = 2.51417
dpAkt = 3.4739
initAkttCFUE = 0.407
initErktCFUE = 1.14
initMektCFUE = 1.46
initPDK1tCFUE = 0.545
initPI3KtCFUE = 0.0127
initPI45P2CFUE = 10.0
initPTENCFUE = 0.0104
initRSKtc = 0.06888
initRaftCFUE = 1.34
initRastCFUE = 3.53
initRpSHIP1 = 0.0
initS6tCFUE = 5.34
initSHIP1tCFUE = 0.0154
initTORC1 = 0.0
kAkt = 9984.96
kPDK1 = 9439.5
kPI3K = 0.000104741
kPI3Kras = 10000.0
kSHIP1 = 0.0745937
kSos = 59.4049
kaRas = 2981.53
kaktinc = 3.468236473
karsk = 1.26435
kas6r = 0.000533083
kas6t = 2180.44
kbackRas = 0.0103384
kbacks6 = 1.00003e-05
kdRas = 0.540777
kdactm = 0.0617342
kdpes = 0.0270729
kdphoss6 = 0.328006
kdrsk = 0.677229
kdt1 = 1588.13
kdt2 = 1e-05
kinrapac = 14.79896824
kinrskc = 100000.0
kmekinc = 7.041474319
kpErk = 9999.08
kpMek = 9774.26
kpRaf = 1.17959
kpes = 0.583255
kppErk = 9999.96
kppMek = 9999.77
ksatc = 0.00197959
kshbasal = 1e-05
kst1 = 20.0908
kst2 = 0.0619403
kvpakt = 0.000174996
kvppErk = 0.000282332
lAkt = 10.1007
lPDK1 = 2355.54
lSHIP1 = 0.000650697
lSos = 0.39616
lpErk = 177.216
lpMek = 0.0414313
lpRaf = 2549.69
lppErk = 3.2516
lppMek = 1336.21
main = 0.00837559
max6c = 0.0833513
n = 4.0
nc = 2.529488566
pEpoRdeactivation = 2.94539
pck1correct = 0.238723
pcoffcorrect = 0.741768
vPI34P2 = 9996.96
vPI45P2 = 84.5564
vPIP3 = 10000.0
vPIP3basal = 0.104429
vpAkt = 6.90774
cyt = 1.0


#initial values
AkttCFUE = 0.407
Epo = 0.002
EpoRCFUE = 0.00416
ErktCFUE = 1.14
GTPRas = 0.06621943788905191
IntpS6 = 0.0
Intpakt = 0.0
Intperk = 0.0
MektCFUE = 1.46
PDK1tCFUE = 0.545
PI3KtCFUE = 0.0127
PI45P2CFUE = 10
PIP3 = 0.015081513956100091
PIP3Akt = 0.3600930213487773
PIP3PDK1 = 0.03106097229240068
PTENCFUE = 0.0104
PhosphatasetCFUE = 0.0415
Proliferation = 0.0
RSKa = 0.0013528078518104567
RSKtc = 0.06888
RaftCFUE = 1.34
Raptorc = 0.1
RastCFUE = 3.53
Rictorc = 0.19886
RpSHIP1 = 0
RpSos = 0.0
S6tCFUE = 5.34
SHIP1tCFUE = 0.0154
TORC1 = 0
TORC2 = 0.0
actPhosphatase = 0.0
mTORa = 0.0
mTORt = 0.1
pAkt = 0.022240698417445963
pEpoR = 0.0
pErk = 0.010253359023255838
pMek = 1.3229314066456617
pRaf = 0.00004103298523818014
pS6 = 0.0001745416822070617
pSos = 0.0
phos2 = 0.0
ppErk = 0.005095166809352595
ppMek = 0.0004062428536835085


#assignment rules
!F pS6plot = 270.9568*pS6