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.