Levchenko2000_MAPK_noScaffold

MAPK cascade in solution (no scaffold)
Description

This model describes a basic 3-
stage Mitogen Activated Protein Kinase (MAPK)
cascade in solution. This cascade is typically expressed as RAF=
=>MEK==>MAPK (alternative forms are K3==>K2==>
K1 and KKK==>KK==>K)
. The input signal is RAFK (RAF Kinase)
and the output signal is MAPKpp (
doubly phosphorylated form of MAPK)
. RAFK phosphorylates RAF once to RAFp. RAFp,
the phosphorylated form of RAF induces two phoshporylations of MEK,
to MEKp and MEKpp. MEKpp,
the doubly phosphorylated form of MEK,
induces two phosphorylations of MAPK to MAPKp and MAPKpp.

Rate constant      
Reaction

a10 = 5.
MAPKPH + MAPKpp -> MAPKppMAPKPH

a1 = 1.
RAF + RAFK -> RAFRAFK

a2 = 0.5
RAFp + RAFPH -> RAFpRAFPH

a3 = 3.3
MEK + RAFp -> MEKRAFp

a4 = 10.
MEKp + MEKPH -> MEKpMEKPH

a5 = 3.3
MEKp + RAFp -> MEKpRAFp

a6 = 10.
MEKPH + MEKpp -> MEKppMEKPH

a7 = 20.
MAPK + MEKpp -> MAPKMEKpp

a8 = 5.
MAPKp + MAPKPH -> MAPKpMAPKPH

a9 = 20.
MAPKp + MEKpp -> MAPKpMEKpp

d10 = 0.4
MAPKppMAPKPH -> MAPKPH + MAPKpp

d1 = 0.4
RAFRAFK -> RAF + RAFK

d2 = 0.5
RAFpRAFPH -> RAFp + RAFPH

d3 = 0.42
MEKRAFp -> MEK + RAFp

d4 = 0.8
MEKpMEKPH -> MEKp + MEKPH

d5 = 0.4
MEKpRAFp -> MEKp + RAFp

d6 = 0.8
MEKppMEKPH -> MEKPH + MEKpp

d7 = 0.6
MAPKMEKpp -> MAPK + MEKpp

d8 = 0.4
MAPKpMAPKPH -> MAPKp + MAPKPH

d9 = 0.6
MAPKpMEKpp -> MAPKp + MEKpp

k10 = 0.1
MAPKppMAPKPH -> MAPKp + MAPKPH

k1 = 0.1
RAFRAFK -> RAFK + RAFp

k2 = 0.1
RAFpRAFPH -> RAF + RAFPH

k3 = 0.1
MEKRAFp -> MEKp + RAFp

k4 = 0.1
MEKpMEKPH -> MEK + MEKPH

k5 = 0.1
MEKpRAFp -> MEKpp + RAFp

k6 = 0.1
MEKppMEKPH -> MEKp + MEKPH

k7 = 0.1
MAPKMEKpp -> MAPKp + MEKpp

k8 = 0.1
MAPKpMAPKPH -> MAPK + MAPKPH

k9 = 0.1
MAPKpMEKpp -> MAPKpp + MEKpp

Variable
IC  
ODE

MAPK
0.3
MAPK'[t] == d7*MAPKMEKpp[t] + k8*MAPKpMAPKPH[t] -
 a7*MAPK[t]*MEKpp[t]

MAPKMEKpp
0
MAPKMEKpp'[t] == -(d7*MAPKMEKpp[t]) - k7*MAPKMEKpp[t]
 + a7*MAPK[t]*MEKpp[t]

MAPKp
0
MAPKp'[t] == k7*MAPKMEKpp[t] - a8*MAPKp[t]*MAPKPH[t]
 + d8*MAPKpMAPKPH[t] + d9*MAPKpMEKpp[t] + k10*
MAPKppMAPKPH[t] - a9*MAPKp[t]*MEKpp[t]

MAPKPH
0.3
MAPKPH'[t] == -(a8*MAPKp[t]*MAPKPH[t]) + d8*MAPKpMAPKPH[
t] + k8*MAPKpMAPKPH[t] - a10*MAPKPH[t]*MAPKpp[t] +
 d10*MAPKppMAPKPH[t] + k10*MAPKppMAPKPH[t]

MAPKpMAPKPH
0
MAPKpMAPKPH'[t] == a8*MAPKp[t]*MAPKPH[t] - d8*
MAPKpMAPKPH[t] - k8*MAPKpMAPKPH[t]

MAPKpMEKpp
0
MAPKpMEKpp'[t] == -(d9*MAPKpMEKpp[t]) - k9*MAPKpMEKpp[t]
 + a9*MAPKp[t]*MEKpp[t]

MAPKpp
0
MAPKpp'[t] == k9*MAPKpMEKpp[t] - a10*MAPKPH[t]*MAPKpp[t]
 + d10*MAPKppMAPKPH[t]

MAPKppMAPKPH
0
MAPKppMAPKPH'[t] == a10*MAPKPH[t]*MAPKpp[t] - d10*
MAPKppMAPKPH[t] - k10*MAPKppMAPKPH[t]

MEK
0.2
MEK'[t] == k4*MEKpMEKPH[t] + d3*MEKRAFp[t] -
 a3*MEK[t]*RAFp[t]

MEKp
0
MEKp'[t] == -(a4*MEKp[t]*MEKPH[t]) + d4*MEKpMEKPH[t]
 + k6*MEKppMEKPH[t] + d5*MEKpRAFp[t] + k3*MEKRAFp[
t] - a5*MEKp[t]*RAFp[t]

MEKPH
0.2
MEKPH'[t] == -(a4*MEKp[t]*MEKPH[t]) + d4*MEKpMEKPH[t]
 + k4*MEKpMEKPH[t] - a6*MEKPH[t]*MEKpp[t] + d6*
MEKppMEKPH[t] + k6*MEKppMEKPH[t]

MEKpMEKPH
0
MEKpMEKPH'[t] == a4*MEKp[t]*MEKPH[t] - d4*MEKpMEKPH[t]
 - k4*MEKpMEKPH[t]

MEKpp
0
MEKpp'[t] == d7*MAPKMEKpp[t] + k7*MAPKMEKpp[t] +
 d9*MAPKpMEKpp[t] + k9*MAPKpMEKpp[t] - a7*MAPK[t]*
MEKpp[t] - a9*MAPKp[t]*MEKpp[t] - a6*MEKPH[t]*MEKpp[t]
 + d6*MEKppMEKPH[t] + k5*MEKpRAFp[t]

MEKppMEKPH
0
MEKppMEKPH'[t] == a6*MEKPH[t]*MEKpp[t] - d6*MEKppMEKPH[
t] - k6*MEKppMEKPH[t]

MEKpRAFp
0
MEKpRAFp'[t] == -(d5*MEKpRAFp[t]) - k5*MEKpRAFp[t]
 + a5*MEKp[t]*RAFp[t]

MEKRAFp
0
MEKRAFp'[t] == -(d3*MEKRAFp[t]) - k3*MEKRAFp[t] +
 a3*MEK[t]*RAFp[t]

RAF
0.4
RAF'[t] == -(a1*RAF[t]*RAFK[t]) + k2*RAFpRAFPH[t] +
 d1*RAFRAFK[t]

RAFK
0.1
RAFK'[t] == -(a1*RAF[t]*RAFK[t]) + d1*RAFRAFK[t] +
 k1*RAFRAFK[t]

RAFp
0
RAFp'[t] == d5*MEKpRAFp[t] + k5*MEKpRAFp[t] +
 d3*MEKRAFp[t] + k3*MEKRAFp[t] - a3*MEK[t]*RAFp[t]
 - a5*MEKp[t]*RAFp[t] - a2*RAFp[t]*RAFPH[t] + d2*
RAFpRAFPH[t] + k1*RAFRAFK[t]

RAFPH
0.3
RAFPH'[t] == -(a2*RAFp[t]*RAFPH[t]) + d2*RAFpRAFPH[t]
 + k2*RAFpRAFPH[t]

RAFpRAFPH
0
RAFpRAFPH'[t] == a2*RAFp[t]*RAFPH[t] - d2*RAFpRAFPH[t]
 - k2*RAFpRAFPH[t]

RAFRAFK
0
RAFRAFK'[t] == a1*RAF[t]*RAFK[t] - d1*RAFRAFK[t] -
 k1*RAFRAFK[t]

Generated by Cellerator Version 1.4.3 (6-March-2004) using Mathematica 5.0
for Mac OS X (November 19, 2003), March 6, 2004 12:18:07, using (PowerMac,
PowerPC,Mac OS X,MacOSX,Darwin)
author=B.E.Shapiro
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team.
For more information see the terms of use
.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.