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Short description

Figure4 and Figure5 can be simulated by Copasi. Figure4 can be simulated in MathSBML as well. There are some typos in the paper:K29=234, is it should k_29; Table2, reaction17, is there are "slash" missing in between the rate equation; reaction 33,"Akt-PI-PP" in the last term of denominator instead of "AktPI-P" . For plotting figure4, we create another extra parameter *_percent, and use assignment rule calculate percentage of each species.

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In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.

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.

Related Publication
  • A computational model on the modulation of mitogen-activated protein kinase (MAPK) and Akt pathways in heregulin-induced ErbB signalling.
  • Hatakeyama M, Kimura S, Naka T, Kawasaki T, Yumoto N, Ichikawa M, Kim JH, Saito K, Saeki M, Shirouzu M, Yokoyama S, Konagaya A
  • The Biochemical journal , 7/ 2003 , Volume 373 , pages: 451-463 , PubMed ID: 12691603
  • RIKEN Genomic Sciences Center, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. marikoh@gsc.riken.go.jp
  • ErbB tyrosine kinase receptors mediate mitogenic signal cascade by binding a variety of ligands and recruiting the different cassettes of adaptor proteins. In the present study, we examined heregulin (HRG)-induced signal transduction of ErbB4 receptor and found that the phosphatidylinositol 3'-kinase (PI3K)-Akt pathway negatively regulated the extracellular signal-regulated kinase (ERK) cascade by phosphorylating Raf-1 on Ser(259). As the time-course kinetics of Akt and ERK activities seemed to be transient and complex, we constructed a mathematical simulation model for HRG-induced ErbB4 receptor signalling to explain the dynamics of the regulation mechanism in this signal transduction cascade. The model reflected well the experimental results observed in HRG-induced ErbB4 cells and in other modes of growth hormone-induced cell signalling that involve Raf-Akt cross-talk. The model suggested that HRG signalling is regulated by protein phosphatase 2A as well as Raf-Akt cross-talk, and protein phosphatase 2A modulates the kinase activity in both the PI3K-Akt and MAPK (mitogen-activated protein kinase) pathways.
Enuo He

Metadata information

BioModels Database MODEL8256371999
BioModels Database BIOMD0000000146
PubMed 12691603
PubMed 11772030
BioModels Database BIOMD0000000019
BioModels Database BIOMD0000000048
BioModels Database BIOMD0000000010
Taxonomy Cricetinae
Gene Ontology ERBB signaling pathway
Mathematical Modelling Ontology Ordinary differential equation model

Curation status

Name Description Size Actions

Model files

BIOMD0000000146_url.xml SBML L2V1 representation of Hatakeyama2003_MAPK 87.92 KB Preview | Download

Additional files

BIOMD0000000146.xpp Auto-generated XPP file 14.26 KB Preview | Download
BIOMD0000000146-biopax2.owl Auto-generated BioPAX (Level 2) 62.68 KB Preview | Download
BIOMD0000000146.vcml Auto-generated VCML file 120.08 KB Preview | Download
BIOMD0000000146.svg Auto-generated Reaction graph (SVG) 100.55 KB Preview | Download
BIOMD0000000146.pdf Auto-generated PDF file 311.61 KB Preview | Download
BIOMD0000000146-biopax3.owl Auto-generated BioPAX (Level 3) 97.95 KB Preview | Download
BIOMD0000000146_urn.xml Auto-generated SBML file with URNs 85.98 KB Preview | Download
BIOMD0000000146.m Auto-generated Octave file 19.67 KB Preview | Download
BIOMD0000000146.sci Auto-generated Scilab file 14.56 KB Preview | Download
BIOMD0000000146.png Auto-generated Reaction graph (PNG) 446.34 KB Preview | Download

  • Model originally submitted by : Enuo He
  • Submitted: Sep 6, 2007 9:06:00 AM
  • Last Modified: May 27, 2014 12:17:39 AM
  • Version: 2 public model Download this version
    • Submitted on: May 27, 2014 12:17:39 AM
    • Submitted by: Enuo He
    • With comment: Current version of Hatakeyama2003_MAPK
  • Version: 1 public model Download this version
    • Submitted on: Sep 6, 2007 9:06:00 AM
    • Submitted by: Enuo He
    • With comment: Original import of Hatakeyama2003_MAPK

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

: Variable used inside SBML models

Species Initial Concentration/Amount

phosphatidylinositol 3-phosphate
800.0 nmol

10.0 nmol

1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate ; IPR015744
0.0 nmol

phosphatidylinositol 3-phosphate ; IPR015744
0.0 nmol

1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate ; IPR015744
0.0 nmol

IPR003527; IPR008349; IPR008350
1000.0 nmol

phosphate(3-) ; IPR008349; phosphate(3-) ; IPR008350
0.0 nmol

diphosphate(4-) ; IPR008349; diphosphate(4-) ; IPR008350
0.0 nmol
GS 10.0 nmol
Reactions Rate Parameters
PIP3 => P_I compartment_0000001*V28*PIP3/(K28+PIP3) V28 = 17000.0; K28 = 9.02
P_I => PIP3; PI3Kstar compartment_0000001*k27*PI3Kstar*P_I/(K27+P_I) K27 = 39.1; k27 = 16.9
PIP3 + Akt => AktPIP3 compartment_0000001*(k29*PIP3*Akt-k_29*AktPIP3) k29 = 507.0; k_29 = 234.0
AktPIP3 => AktPIP compartment_0000001*V30*AktPIP3/(K30*(1+AktPIP/K32)+AktPIP3) V30 = 20000.0; K30 = 80000.0; K32 = 80000.0
AktPIP => AktPIP3; MEKP, MEKPP, AktPIPP, PP2A compartment_0000001*k31*PP2A*AktPIP/(K31*(1+MEKP/K16+MEKPP/K18+AktPIPP/K33)+AktPIP) K16 = 2200.0; K33 = 12.0; K18 = 60.0; k31 = 0.107; K31 = 4.35
AktPIP => AktPIPP; AktPIP3 compartment_0000001*V32*AktPIP/(K32*(1+AktPIP3/K30)+AktPIP) K30 = 80000.0; K32 = 80000.0; V32 = 20000.0
AktPIPP => AktPIP; MEKP, MEKPP, PP2A compartment_0000001*k33*PP2A*AktPIPP/(K33*(1+MEKP/K16+MEKPP/K18+AktPIP/K31)+AktPIPP) K33 = 12.0; K16 = 2200.0; K18 = 60.0; K31 = 4.35; k33 = 0.211
ERK => ERKP; MEKPP compartment_0000001*k19*MEKPP*ERK/(K19*(1+ERKP/K21)+ERK) K19 = 146000.0; K21 = 146000.0; k19 = 9.5
ERKP => ERK; ERKPP, MKP3 compartment_0000001*k20*MKP3*ERKP/(K20*(1+ERKPP/K22)+ERKP) K22 = 60.0; K20 = 160.0; k20 = 0.3
ERKPP => ERKP; MKP3 compartment_0000001*k22*MKP3*ERKPP/(K22*(1+ERKP/K20)+ERKPP) K22 = 60.0; K20 = 160.0; k22 = 0.27
RShP + GS => RShGS compartment_0000001*(k7*RShP*GS-k_7*RShGS) k_7 = 546.0; k7 = 60.0
Curator's comment:
(added: 28 Aug 2007, 00:16:43, updated: 28 Aug 2007, 00:16:43)
Figure4 has been reproduced by MathSBML.