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BIOMD0000000011 - Levchenko2000_MAPK_noScaffold

 

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Reference Publication
Publication ID: 10823939
Levchenko A, Bruck J, Sternberg PW.
Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties.
Proc. Natl. Acad. Sci. U.S.A. 2000 May; 97(11): 5818-5823
Division of Engineering and Applied Science and Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA. andre@paradise.caltech.edu  [more]
Model
Original Model: BIOMD0000000011.xml.origin
Submitter: Nicolas Le Novère
Submission ID: MODEL6615234250
Submission Date: 13 Sep 2005 12:41:40 UTC
Last Modification Date: 03 Jun 2013 13:36:09 UTC
Creation Date: 15 Feb 2005 00:12:30 UTC
Encoders:  Bruce Shapiro
set #1
bqbiol:occursIn Taxonomy Xenopus laevis
set #2
bqbiol:isVersionOf Gene Ontology MAPK cascade
bqbiol:isHomologTo Reactome REACT_634
set #3
bqmodel:isDerivedFrom BioModels Database Huang1996 - Ultrasensitivity in MAPK cascade
PubMed 6501300
PubMed 6947258
Notes

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.

Model
Publication ID: 10823939 Submission Date: 13 Sep 2005 12:41:40 UTC Last Modification Date: 03 Jun 2013 13:36:09 UTC Creation Date: 15 Feb 2005 00:12:30 UTC
Mathematical expressions
Reactions
binding of RAF and RAFK dissociation of RAF_RAFK phosphorylation of RAF binding of RAF-P and RAF phosphatase
dissociation of RAF-P_RAFPase dephosphorylation of RAF-P binding of MEK and RAF-P dissociation of MEK_RAF-P
phosphorylation of MEK binding of MEK-P and MEK phosphatase dissociation of MEK-P_MEKPase dephosphorylation of MEK-P
binding of MEK-P and RAF-P dissociation of MEK-P_RAF-P phosphorylation of MEK-P binding of MEK-PP and MEK phosphatase
dissociation of MEK-PP_MEKPase dephosphorylation of MEK-PP binding of MAPK and MEK-PP dissociation of MAPK_MEK-PP
phosphorylation of MAPK binding of MAPK-P and MAPK phosphatase dissociation of MAPK-P_MAPKPase dephosphorylation of MAPK-P
binding of MAPK-P and MEK-PP dissociation of MAPK-P_MEK-PP phosphorylation of MAPK-P binding of MAPK-PP and MAPK phosphatase
dissociation of MAPK-PP_MAPKPase dephosphorylation of MAPK-PP    
Physical entities
Compartments Species
Cytoplasm MAPK MAPK_MEK-PP MAPK-P
MAPK phosphatase MAPK-P_MAPKPase MAPK-P_MEK-PP
MAPK-PP MAPK-PP_MAPKPase MEK
MEK-P MEK phosphatase MEK-P_MEKPase
MEK-PP MEK-PP_MEKPase MEK-P_RAF-P
MEK_RAF-P RAF RAFK
RAF-P RAF phosphatase RAF-P_RAFPase
RAF_RAFK    
Reactions (30)
 
 binding of RAF and RAFK [RAF] + [RAFK] → [RAF_RAFK];  
 
 dissociation of RAF_RAFK [RAF_RAFK] → [RAF] + [RAFK];  
 
 phosphorylation of RAF [RAF_RAFK] → [RAFK] + [RAF-P];  
 
 binding of RAF-P and RAF phosphatase [RAF-P] + [RAF phosphatase] → [RAF-P_RAFPase];  
 
 dissociation of RAF-P_RAFPase [RAF-P_RAFPase] → [RAF-P] + [RAF phosphatase];  
 
 dephosphorylation of RAF-P [RAF-P_RAFPase] → [RAF] + [RAF phosphatase];  
 
 binding of MEK and RAF-P [MEK] + [RAF-P] → [MEK_RAF-P];  
 
 dissociation of MEK_RAF-P [MEK_RAF-P] → [MEK] + [RAF-P];  
 
 phosphorylation of MEK [MEK_RAF-P] → [MEK-P] + [RAF-P];  
 
 binding of MEK-P and MEK phosphatase [MEK-P] + [MEK phosphatase] → [MEK-P_MEKPase];  
 
 dissociation of MEK-P_MEKPase [MEK-P_MEKPase] → [MEK-P] + [MEK phosphatase];  
 
 dephosphorylation of MEK-P [MEK-P_MEKPase] → [MEK] + [MEK phosphatase];  
 
 binding of MEK-P and RAF-P [MEK-P] + [RAF-P] → [MEK-P_RAF-P];  
 
 dissociation of MEK-P_RAF-P [MEK-P_RAF-P] → [MEK-P] + [RAF-P];  
 
 phosphorylation of MEK-P [MEK-P_RAF-P] → [MEK-PP] + [RAF-P];  
 
 binding of MEK-PP and MEK phosphatase [MEK phosphatase] + [MEK-PP] → [MEK-PP_MEKPase];  
 
 dissociation of MEK-PP_MEKPase [MEK-PP_MEKPase] → [MEK phosphatase] + [MEK-PP];  
 
 dephosphorylation of MEK-PP [MEK-PP_MEKPase] → [MEK-P] + [MEK phosphatase];  
 
 binding of MAPK and MEK-PP [MAPK] + [MEK-PP] → [MAPK_MEK-PP];  
 
 dissociation of MAPK_MEK-PP [MAPK_MEK-PP] → [MAPK] + [MEK-PP];  
 
 phosphorylation of MAPK [MAPK_MEK-PP] → [MAPK-P] + [MEK-PP];  
 
 binding of MAPK-P and MAPK phosphatase [MAPK-P] + [MAPK phosphatase] → [MAPK-P_MAPKPase];  
 
 dissociation of MAPK-P_MAPKPase [MAPK-P_MAPKPase] → [MAPK-P] + [MAPK phosphatase];  
 
 dephosphorylation of MAPK-P [MAPK-P_MAPKPase] → [MAPK] + [MAPK phosphatase];  
 
 binding of MAPK-P and MEK-PP [MAPK-P] + [MEK-PP] → [MAPK-P_MEK-PP];  
 
 dissociation of MAPK-P_MEK-PP [MAPK-P_MEK-PP] → [MAPK-P] + [MEK-PP];  
 
 phosphorylation of MAPK-P [MAPK-P_MEK-PP] → [MAPK-PP] + [MEK-PP];  
 
 binding of MAPK-PP and MAPK phosphatase [MAPK phosphatase] + [MAPK-PP] → [MAPK-PP_MAPKPase];  
 
 dissociation of MAPK-PP_MAPKPase [MAPK-PP_MAPKPase] → [MAPK phosphatase] + [MAPK-PP];  
 
 dephosphorylation of MAPK-PP [MAPK-PP_MAPKPase] → [MAPK-P] + [MAPK phosphatase];  
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 MAPK
Compartment: Cytoplasm
Initial amount: 0.4
 
 MAPK_MEK-PP
Compartment: Cytoplasm
Initial amount: 0.0
 
 MAPK-P
Compartment: Cytoplasm
Initial amount: 0.0
 
 MAPK phosphatase
Compartment: Cytoplasm
Initial amount: 0.3
 
 MAPK-P_MAPKPase
Compartment: Cytoplasm
Initial amount: 0.0
 
 MAPK-P_MEK-PP
Compartment: Cytoplasm
Initial amount: 0.0
 
 MAPK-PP
Compartment: Cytoplasm
Initial amount: 0.0
 
 MAPK-PP_MAPKPase
Compartment: Cytoplasm
Initial amount: 0.0
 
 MEK
Compartment: Cytoplasm
Initial amount: 0.2
 
 MEK-P
Compartment: Cytoplasm
Initial amount: 0.0
 
   MEK phosphatase
Compartment: Cytoplasm
Initial amount: 0.2
 
 MEK-P_MEKPase
Compartment: Cytoplasm
Initial amount: 0.0
 
 MEK-PP
Compartment: Cytoplasm
Initial amount: 0.0
 
 MEK-PP_MEKPase
Compartment: Cytoplasm
Initial amount: 0.0
 
 MEK-P_RAF-P
Compartment: Cytoplasm
Initial amount: 0.0
 
 MEK_RAF-P
Compartment: Cytoplasm
Initial amount: 0.0
 
 RAF
Compartment: Cytoplasm
Initial amount: 0.3
 
 RAFK
Compartment: Cytoplasm
Initial amount: 0.2
 
 RAF-P
Compartment: Cytoplasm
Initial amount: 0.0
 
   RAF phosphatase
Compartment: Cytoplasm
Initial amount: 0.3
 
 RAF-P_RAFPase
Compartment: Cytoplasm
Initial amount: 0.0
 
 RAF_RAFK
Compartment: Cytoplasm
Initial amount: 0.0
 
binding of RAF and RAFK (1)
 
   a1
Value: 1.0
Constant
 
dissociation of RAF_RAFK (1)
 
   d1
Value: 0.4
Constant
 
phosphorylation of RAF (1)
 
   k1
Value: 0.1
Constant
 
binding of RAF-P and RAF phosphatase (1)
 
   a2
Value: 0.5
Constant
 
dissociation of RAF-P_RAFPase (1)
 
   d2
Value: 0.5
Constant
 
dephosphorylation of RAF-P (1)
 
   k2
Value: 0.1
Constant
 
binding of MEK and RAF-P (1)
 
   a3
Value: 3.3
Constant
 
dissociation of MEK_RAF-P (1)
 
   d3
Value: 0.42
Constant
 
phosphorylation of MEK (1)
 
   k3
Value: 0.1
Constant
 
binding of MEK-P and MEK phosphatase (1)
 
   a4
Value: 10.0
Constant
 
dissociation of MEK-P_MEKPase (1)
 
   d4
Value: 0.8
Constant
 
dephosphorylation of MEK-P (1)
 
   k4
Value: 0.1
Constant
 
binding of MEK-P and RAF-P (1)
 
   a5
Value: 3.3
Constant
 
dissociation of MEK-P_RAF-P (1)
 
   d5
Value: 0.4
Constant
 
phosphorylation of MEK-P (1)
 
   k5
Value: 0.1
Constant
 
binding of MEK-PP and MEK phosphatase (1)
 
   a6
Value: 10.0
Constant
 
dissociation of MEK-PP_MEKPase (1)
 
   d6
Value: 0.8
Constant
 
dephosphorylation of MEK-PP (1)
 
   k6
Value: 0.1
Constant
 
binding of MAPK and MEK-PP (1)
 
   a7
Value: 20.0
Constant
 
dissociation of MAPK_MEK-PP (1)
 
   d7
Value: 0.6
Constant
 
phosphorylation of MAPK (1)
 
   k7
Value: 0.1
Constant
 
binding of MAPK-P and MAPK phosphatase (1)
 
   a8
Value: 5.0
Constant
 
dissociation of MAPK-P_MAPKPase (1)
 
   d8
Value: 0.4
Constant
 
dephosphorylation of MAPK-P (1)
 
   k8
Value: 0.1
Constant
 
binding of MAPK-P and MEK-PP (1)
 
   a9
Value: 20.0
Constant
 
dissociation of MAPK-P_MEK-PP (1)
 
   d9
Value: 0.6
Constant
 
phosphorylation of MAPK-P (1)
 
   k9
Value: 0.1
Constant
 
binding of MAPK-PP and MAPK phosphatase (1)
 
   a10
Value: 5.0
Constant
 
dissociation of MAPK-PP_MAPKPase (1)
 
   d10
Value: 0.4
Constant
 
dephosphorylation of MAPK-PP (1)
 
   k10
Value: 0.1
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000011

Curator's comment: (updated: 26 Nov 2010 04:31:48 GMT)

Reproduction of the signal-response curve of the model without scaffolding from figure 2 C. The calculations were performed using the parameter scan task of Copasi 4.6. The initial concentration of RAFK was varied from 0 to 2 uM with 100 intervals and a time course run over 100 sec at each. The concentration of MAPK-PP was integrated over the range of the whole time course.

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