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BIOMD0000000251 - Nakakuki2010_CellFateDecision_Core

 

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Reference Publication
Publication ID: 20493519
Nakakuki T, Birtwistle MR, Saeki Y, Yumoto N, Ide K, Nagashima T, Brusch L, Ogunnaike BA, Okada-Hatakeyama M, Kholodenko BN.
Ligand-specific c-Fos expression emerges from the spatiotemporal control of ErbB network dynamics.
Cell 2010 May; 141(5): 884-896
Computational Systems Biology Research Group, Advanced Computational Sciences Department, RIKEN Advanced Science Institute, 1-7-22 Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.  [more]
Model
Original Model: core model of publication ...
Submitter: Lutz Brusch
Submission ID: MODEL1003170000
Submission Date: 17 Mar 2010 16:31:18 UTC
Last Modification Date: 03 Jun 2014 15:00:12 UTC
Creation Date: 24 May 2010 11:49:05 UTC
Encoders:  Lukas Endler
   Lutz Brusch
set #1
bqmodel:isDerivedFrom BioModels Database Birtwistle2007_ErbB_Signalling
PubMed 12242336
set #2
bqbiol:hasVersion Gene Ontology epidermal growth factor receptor signaling pathway via MAPK cascade
Gene Ontology obsolete MAPKKK cascade involved in epidermal growth factor receptor signaling
bqbiol:isPartOf KEGG Pathway MAPK signaling pathway - Homo sapiens (human)
bqbiol:isVersionOf Reactome REACT_9417
bqbiol:hasTaxon Taxonomy Homo sapiens
set #3
bqbiol:hasVersion Reactome REACT_634
Notes

This model describes the activation of immediate early genes such as cFos after EGF or heregulin (HRG) stimulation of the MAPK pathway. Phosphorylated cFos is a key transcription factor triggering downstream cascades of cell fate determination. The model can explain how the switch-like response of p-cFos emerges from the spatiotemporal dynamics. The model comprises lumped reaction kinetics of the signal transduction pathway, the transcriptional and the posttranslational feedback and feedforward loops. The parameter set implemented here corresponds to that used for generating Figs. 4 B,C,D (red curves for 10nM HRG) of the below article in Cell (2010). Moreover, we found that the same model described well the dynamics in different cell types (MCF-7 and PC-12), of different ligands (EGF and HRG) and at different doses (0.1nM, 1nM, 10nM) for a unique set of parameter values (as implemented here and reported in Table SD4_1 of the article) except for four parameters characterising the input, cytoplasmic ppERK. These four parameters K1, K2, tau1 and tau2 are used in the two equations involving species x1 and x2. These two equations define a phenomenological input module to describe the ligand-, dose- and cell type-dependent dynamics of ppERKc which are not modelled in mechanistic detail here. The four parameter values can be adjusted to model a specific ligand, dose and cell type. 8 parameter sets for different experiments are given in Table SD4_2 of the article. This SBML file, however, carries just one such parameter set. We have chosen that of MCF-7 cells stimulated by 10nM of HRG. To reproduce all simulations from the article, please replace the parameter values for K1, K2, tau1, tau2 as needed.

Ligand-specific c-Fos expression emerges from the spatiotemporal control of ErbB network dynamics.
Takashi Nakakuki(1), Marc R. Birtwistle(2,3,4), Yuko Saeki(1,5), Noriko Yumoto(1,5), Kaori Ide(1), Takeshi Nagashima(1,5), Lutz Brusch(6), Babatunde A. Ogunnaike(3), Mariko Hatakeyama(1,5), and Boris N. Kholodenko(2,4); Cell In Press, online 20 May 2010, doi:10.1016/j.cell.2010.03.054
(1) RIKEN Advanced Science Institute, Computational Systems Biology Research Group, Advanced Computational Sciences Department, 1-7-22 Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan
(2) Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland
(3) University of Delaware, Department of Chemical Engineering, 150 Academy St., Newark, DE 19716, USA
(4) Thomas Jefferson University, Department of Pathology, Anatomy, and Cell Biology, 1020 Locust Street, Philadelphia, PA 19107, USA
(5) RIKEN Research Center for Allergy and Immunology, Laboratory for Cellular Systems Modeling, 1-7-22 Tsurumi-ku, Yokohama, 230-0045, Japan
(6) Dresden University of Technology, Center for Information Services and High Performance Computing, 01062 Dresden, Germany

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 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: 20493519 Submission Date: 17 Mar 2010 16:31:18 UTC Last Modification Date: 03 Jun 2014 15:00:12 UTC Creation Date: 24 May 2010 11:49:05 UTC
Mathematical expressions
Reactions
1 PhIM 1 1 PhIM 2 2a ppERKn 2b DUSP
3 pRSKn 4 cFOSp 5 cFOSm 6 cFOS
7 pcFOS      
Rules
Assignment Rule (variable: ppERK(cytosol))      
Physical entities
Compartments Species
compartment x1 x2 ppERK(nucleus)
DUSP pRSKn cFOS preRNA
cFOS pc-FOS cFOSmRNA
ppERK(cytosol)    
Global parameters
k7 k11 k13 L
K1 tau1 K tau
Reactions (9)
 
 1 PhIM 1  → [x1];  
 
 1 PhIM 2  → [x2];  
 
 2a ppERKn  → [ppERK(nucleus)];   {ppERK(cytosol)} , {DUSP}
 
 2b DUSP  → [DUSP];   {ppERK(nucleus)}
 
 3 pRSKn  → [pRSKn];   {ppERK(nucleus)}
 
 4 cFOSp  → [cFOS preRNA];   {ppERK(nucleus)} , {pRSKn}
 
 5 cFOSm  → [cFOSmRNA];   {cFOS preRNA}
 
 6 cFOS  → [cFOS];   {cFOSmRNA} , {ppERK(cytosol)} , {pc-FOS}
 
 7 pcFOS  → [pc-FOS];   {cFOS} , {ppERK(cytosol)}
 
Rules (1)
 
 Assignment Rule (name: ppERKc) ppERK(cytosol) = x1-x2
 
 compartment Spatial dimensions: 3.0  Compartment size: 1.0
 
 x1
Compartment: compartment
Initial concentration: 0.0
 
 x2
Compartment: compartment
Initial concentration: 0.0
 
 ppERK(nucleus)
Compartment: compartment
Initial concentration: 0.0
 
 DUSP
Compartment: compartment
Initial concentration: 0.0
 
 pRSKn
Compartment: compartment
Initial concentration: 0.0
 
 cFOS preRNA
Compartment: compartment
Initial concentration: 0.0
 
 cFOS
Compartment: compartment
Initial concentration: 0.0
 
 pc-FOS
Compartment: compartment
Initial concentration: 0.0
 
 cFOSmRNA
Compartment: compartment
Initial concentration: 0.0
 
  ppERK(cytosol)
Compartment: compartment
 
Global Parameters (8)
 
   k7
Value: 0.5
Constant
 
   k11
Value: 0.11
Constant
 
   k13
Value: 0.06
Constant
 
   L
Value: 1.0
Constant
 
   K1
Value: 1.09
Constant
 
   tau1
Value: 3.07
Constant
 
   K
Value: 2.89
Constant
 
   tau
Value: 472.0
Constant
 
2a ppERKn (3)
 
   k1
Value: 15.0
Constant
 
   k2
Value: 50.0
Constant
 
   k3
Value: 14.0
Constant
 
2b DUSP (1)
 
   k
Value: 1.0
Constant
 
3 pRSKn (2)
 
   k4
Value: 0.1
Constant
 
   k5
Value: 0.15
Constant
 
4 cFOSp (2)
 
   k6
Value: 0.13
Constant
 
   n
Value: 1.1
Constant
 
5 cFOSm (1)
 
   k8
Value: 0.08
Constant
 
6 cFOS (2)
 
   k10
Value: 0.3
Constant
 
   k9
Value: 0.3
Constant
 
7 pcFOS (1)
 
   k12
Value: 0.001
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000251

Curator's comment: (updated: 24 May 2010 12:48:21 BST)

reproduction of the 10 nM HRG stimlations depicted in figures 4BCD of the original publication. The results were obtained using SBML ODESolver.

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