#adlung3



#reactions
v1:
 {1.0}BaF3Epo = $pool
  Epodegradation * BaF3Epo
v18:
 $pool = {1.0}RpSHIP1
  kSHIP1 * (SHIP1t32D - RpSHIP1) * (pEpoR - RpSHIP1)
v19:
 {1.0}RpSHIP1 = $pool
  lSHIP1 * RpSHIP1
v2:
 $pool = {1.0}pEpoR
  EpoRactivation1 / (1 + phos2 / Ki1) * (EpoR32D - pEpoR * (1 + kPI3K / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) + kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1))) * (pow(BaF3Epo, nb) / (pow(ksatb, nb) + pow(BaF3Epo, nb)))
v20:
 $pool = {1.0}PIP3
  vPIP3 * PI45P232D * kPI3K / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR
v21:
 $pool = {1.0}PIP3
  vPIP3 * main1 * PI45P232D * kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR
v22:
 {1.0}PIP3 = $pool
  kshbasal * PIP3 * (SHIP1t32D - RpSHIP1)
v23:
 {1.0}PIP3 = $pool
  vPI45P2 * PIP3 * PTEN32D
v24:
 {1.0}PIP3 = $pool
  vPI34P2 * PIP3 * RpSHIP1
v25:
 {1.0}PIP3 = {1.0}PIP3PDK1
  kPDK1 * PIP3 * (PDK1t32D - PIP3PDK1)
v26:
 {1.0}PIP3PDK1 = {1.0}PIP3
  lPDK1 * PIP3PDK1
v27:
 {1.0}PIP3 = {1.0}PIP3Akt
  kAkt * PIP3 * (Aktt32D - PIP3Akt - pAkt)
v28:
 {1.0}PIP3Akt = {1.0}PIP3
  lAkt * PIP3Akt
v29:
 {1.0}PIP3Akt = $pool
  vpAkt * PIP3Akt * PIP3PDK1
v3:
 $pool = {1.0}actPhosphatase
  Phosphataseactivation1 * (Phosphataset32D - actPhosphatase) * pEpoR
v30:
 $pool = {1.0}PIP3
  vpAkt * PIP3Akt * PIP3PDK1
v31:
 $pool = {1.0}pAkt
  vpAkt * PIP3Akt * PIP3PDK1 / (1 + kaktind * Aktin)
v32:
 {1.0}pAkt = $pool
  dpAkt * pAkt
v33:
 $pool = {1.0}PIP3
  vPIP3basal * PI45P232D * (PI3Kt32D - kPI3K / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR - kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR)
v34:
 $pool = {1.0}PIP3
  vPIP3basal * main1 * PI45P232D
v35:
 $pool = {1.0}pSos
  kpes * (Sostb - pSos - RpSos) * ppErk
v36:
 {1.0}pSos = $pool
  kdpes * pSos
v37:
 $pool = {1.0}RpSos
  kSos * (Sostb - RpSos - pSos) * (pEpoR - RpSos)
v38:
 {1.0}RpSos = $pool
  lSos * RpSos
v39:
 {1.0}RpSos = {1.0}pSos
  kpes * RpSos * ppErk
v4:
 {1.0}actPhosphatase = $pool
  Phosphatasedeactivation1 * actPhosphatase
v40:
 $pool = {1.0}GTPRas
  kbackRas * (Rast32D - GTPRas - kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR)
v41:
 $pool = {1.0}GTPRas
  kaRas * RpSos * (Rast32D - GTPRas - kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR)
v42:
 {1.0}GTPRas = $pool
  kdRas * GTPRas
v43:
 $pool = {1.0}pRaf
  kpRaf * (GTPRas + kPI3K * kPI3Kras / ((1 + kPI3K) * 1 + kPI3K * kPI3Kras * 1) * pEpoR) * (Raft32D - pRaf)
v44:
 {1.0}pRaf = $pool
  lpRaf * pRaf
v45:
 $pool = {1.0}pMek
  kpMek * pRaf * (Mekt32D - pMek - ppMek)
v46:
 {1.0}pMek = $pool
  lpMek * pMek
v47:
 {1.0}pMek = {1.0}ppMek
  kppMek * pRaf * pMek
v48:
 {1.0}ppMek = {1.0}pMek
  lppMek * ppMek
v49:
 $pool = {1.0}pErk
  kpErk * ppMek * (Erkt32D - pErk - ppErk)
v5:
 {1.0}pEpoR = $pool
  pEpoRdeactivation1 * pEpoR * actPhosphatase
v50:
 {1.0}pErk = $pool
  lpErk * dDUSP3 * pErk
v51:
 {1.0}pErk = {1.0}ppErk
  kppErk * ppMek * pErk / (1 + kmekind * Mekin)
v52:
 {1.0}ppErk = {1.0}pErk
  lppErk * dDUSP3 * ppErk
v53:
 $pool = {1.0}Intperk
  ppErk
v54:
 $pool = {1.0}Intpakt
  pAkt
v55:
 $pool = {1.0}mTORa
  kvpakt * pAkt * (mTORt - mTORa - TORC1 - TORC2)
v56:
 $pool = {1.0}mTORa
  kvppErk * RSKa / (1 + kinrskb * RSKin) * (mTORt - mTORa - TORC1 - TORC2)
v57:
 {1.0}mTORa = $pool
  kdactm * mTORa
v58:
 {1.0}mTORa = {1.0}TORC1
  kst1 / (1 + kinrapab * Rapamycin) * (mTORa - TORC1 - TORC2) * (Raptord - TORC1)
v59:
 {1.0}TORC1 = {1.0}mTORa
  kdt1 * TORC1
v6:
 $pool = {1.0}phos2
  Phosact1 * pow(pEpoR, n1) / (pow(Ji1, n1) + pow(pEpoR, n1))
v60:
 {1.0}TORC1 = $pool
  kdactm * TORC1
v61:
 {1.0}mTORa = {1.0}TORC2
  kst2 * (mTORa - TORC2 - TORC1) * (Rictord - TORC2)
v62:
 {1.0}TORC2 = {1.0}mTORa
  kdt2 * TORC2
v63:
 {1.0}TORC2 = $pool
  kdactm * TORC2
v64:
 $pool = {1.0}RSKa
  karsk / (1 + kinrskb * RSKin) * (RSKtd - RSKa) * ppErk
v65:
 {1.0}RSKa = $pool
  kdrsk * RSKa
v66:
 $pool = {1.0}pS6
  kas6t * TORC1 * (S6t32D - pS6)
v67:
 $pool = {1.0}pS6
  kas6r * RSKa * (S6t32D - pS6)
v68:
 $pool = {1.0}pS6
  kbacks6 * (S6t32D - pS6)
v69:
 {1.0}pS6 = $pool
  kdphoss6 * pS6
v7:
 {1.0}phos2 = $pool
  Phosdeact1 * phos2
v70:
 $pool = {1.0}Proliferation
  pdk2correct * ((cycleaktind * pAkt + cyclemekind * ppErk) / maxccd) + pdoffcorrect / 60
v71:
 $pool = {1.0}IntpS6
  pS6


#parameters
Aktin = 0.0
EpoRactivation1 = 0.140964
Epodegradation = 0.0173287
Ji1 = 0.220505
Ki1 = 0.0272784
Mekin = 0.0
Phosact1 = 341.317
Phosdeact1 = 1e-05
Phosphataseactivation1 = 144.425
Phosphatasedeactivation1 = 1e-05
RSKin = 0.0
Rapamycin = 0.0
Sostb = 4.46181e-05
cycleaktind = 0.551765
cyclemekind = 0.0331257
dDUSP3 = 96.7609
dpAkt = 3.4739
initAktt32D = 0.60774
initErkt32D = 2.3261
initMekt32D = 4.7439
initPDK1t32D = 1.5545
initPI3Kt32D = 0.0124
initPI45P232D = 10.0
initPTEN32D = 0.096799
initRSKtd = 1.6972
initRaft32D = 7.8073
initRast32D = 7.8554
initRpGab2PI3K = 0.0
initRpPI3K = 0.0
initRpSHIP1 = 0.0
initS6t32D = 4.5318
initSHIP1t32D = 0.12778
initTORC1 = 0.0
kAkt = 9984.96
kPDK1 = 9439.5
kPI3K = 0.000104741
kPI3Kras = 10000.0
kSHIP1 = 0.0745937
kSos = 59.4049
kaRas = 2981.53
kaktind = 2.054443007
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
kinrapab = 2.778901656
kinrskb = 0.552054462
kmekind = 0.500416844
kpErk = 9999.08
kpMek = 9774.26
kpRaf = 1.17959
kpes = 0.583255
kppErk = 9999.96
kppMek = 9999.77
ksatb = 0.0024577
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
main1 = 0.000224787
maxccd = 0.88
n1 = 4.0
nb = 2.03939
pEpoRdeactivation1 = 3.20488
pdk2correct = 0.264415
pdoffcorrect = 0.641853
vPI34P2 = 9996.96
vPI45P2 = 84.5564
vPIP3 = 10000.0
vPIP3basal = 0.104429
vpAkt = 6.9
cyt = 1.0


#initial values
Aktt32D = 0.60774
BaF3Epo = 0.02
EpoR32D = 0.016766
Erkt32D = 2.3261
GTPRas = 0.14735982220783525
IntpS6 = 0.0
Intpakt = 0.0
Intperk = 0.0
Mekt32D = 4.7439
PDK1t32D = 1.5545
PI3Kt32D = 0.0124
PI45P232D = 10
PIP3 = 0.0015820688561687386
PIP3Akt = 0.3654172114157491
PIP3PDK1 = 0.00979331927840607
PTEN32D = 0.096799
Phosphataset32D = 0.0415
Proliferation = 0.0
RSKa = 0.09656086787310815
RSKtd = 1.6972
Raft32D = 7.8073
Raptord = 0.1
Rast32D = 7.8554
Rictord = 0.099259
RpSHIP1 = 0.0
RpSos = 0.0
S6t32D = 4.5318
SHIP1t32D = 0.12778
TORC1 = 0.0
TORC2 = 0.0
actPhosphatase = 0.0
mTORa = 0.0
mTORt = 0.1
pAkt = 0.007108053543974432
pEpoR = 0.0
pErk = 0.024884819917878956
pMek = 4.687884851008414
pRaf = 0.0005320136586637678
pS6 = 0.0008491959467671434
pSos = 0.0
phos2 = 0.0
ppErk = 0.014762189034818775
ppMek = 0.018664442030427147


#assignment rules
!F pS6plot = 532.9197*pS6