COPASI6
is: REACT 13229.1
type: Species
constant: false
name: pRSKn
is: SBO:0000252
in compartment: 143010
initial amount: NaN
boundary condition: false
initial concentration: 0.0
has only substance units: false

143175
kinetic law: 027056
product: 027019
fast: false
has part: GO:0000189
name: 2a ppERKn
type: Reaction
reversible: false
has part: GO:0017017
has part: REACT 1866
modifier: 027044
has part: REACT_12439
has part: REACT 487
modifier: 027031

027069
stoichiometry: 1.0
species: COPASI5
type: SpeciesReference

143185
value: 15.0
name: k1
type: LocalParameter

027105
stoichiometry: 1.0
species: COPASI6
type: SpeciesReference

143203
constant: true
value: 0.5
name: k7
type: Parameter

COPASI7
boundary condition: false
is: SBO:0000250
initial amount: NaN
initial concentration: 0.0
is encoded by: hsa:2353
has only substance units: false
type: Species
name: cFOS preRNA
constant: false
encodes: REACT 21788.1
in compartment: 143010

027019
stoichiometry: 1.0
species: COPASI4
type: SpeciesReference

026971
stoichiometry: 1.0
species: COPASI2
type: SpeciesReference

143186
value: 50.0
name: k2
type: LocalParameter

143195
value: 0.3
name: k10
type: LocalParameter

143204
constant: true
value: 0.11
name: k11
type: Parameter

COPASI4
in compartment: 143010
boundary condition: false
is version of: REACT 13301.1
has only substance units: false
is version of: P27361
is version of: P28482
type: Species
constant: false
is: SBO:0000252
is version of: C00562
initial amount: NaN
name: ppERK(nucleus)
initial concentration: 0.0

143193
value: 0.08
name: k8
type: LocalParameter

026935
exponent: 1.0
scale: 0
multipler: 60.0
kind: SECOND
type: SBMLUnit

143173
kinetic law: 026983
product: 026971
is version of: GO:0000187
fast: false
reversible: false
name: 1 PhIM 1
type: Reaction

143187
value: 14.0
name: k3
type: LocalParameter

COPASI5
is version of: Q13202
has only substance units: false
initial concentration: 0.0
name: DUSP
is version of: IPR014393
is version of: Q05923
is version of: Q16690
type: Species
boundary condition: false
constant: false
is: SBO:0000252
is version of: REACT 12976.1
initial amount: NaN
is version of: P28562
is version of: Q13115
is version of: Q9Y6W6
in compartment: 143010
is homolog to: K04459

027288
stoichiometry: 1.0
species: COPASI9
type: SpeciesReference

143192
value: 1.1
name: n
type: LocalParameter

027141
stoichiometry: 1.0
species: COPASI7
type: SpeciesReference

143174
kinetic law: 027007
product: 026995
is version of: GO:0043407
fast: false
reversible: false
name: 1 PhIM 2
type: Reaction

BIOMD0000000251
curated: true
reaction: 143182
created:
  W3 CDTF: Mon May 24 12:49:05 BST 2010
units def: 026923
is: MODEL1003170000
occurs in: http://identifiers.org/taxonomy/9606
volume units: 026899
is version of: REACT 9417
parameter: 143213
species: COPASI4
reaction: 143175
species: COPASI10
species: COPASI3
species: COPASI7
reaction: 143181
creator:
  ORG:
    orgname: Dresden University of Technology
  n:
    given: Lutz
    family: Brusch
parameter: 143212
units def: 026899
has version: REACT 634
reaction: 143179
parameter: 143209
compartment: 143010
reaction: 143173
reaction: 143174
modified:
  W3 CDTF: Fri Mar 16 23:37:35 GMT 2012
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 Hatake…
parameter: 143203
area units: metaid_0000005
parameter: 143204
species: COPASI5
is part of: hsa04010
species: COPASI8
parameter: 143211
units def: 026947
has version: GO:0038029
reaction: 143183
rule: 143201
reaction: 143177
reaction: 143178
parameter: 143207
parameter: 143208
is described by: http://identifiers.org/pubmed/20493519
has version: GO:0035559
time units: 026923
name: Nakakuki2010_CellFateDecision_Core
species: COPASI2
type: SBMLModel
species: COPASI6
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Lukas
    family: Endler
substance units: 026947
species: 143172
length unit: length
species: COPASI9

143188
value: 1.0
name: k
type: LocalParameter

143199
value: 0.001
name: k12
type: LocalParameter

143191
value: 0.13
name: k6
type: LocalParameter

027190
stoichiometry: 1.0
species: COPASI10
type: SpeciesReference

143172
is version of: REACT 2640
type: Species
is: SBO:0000252
is version of: C00562
constant: false
has only substance units: false
initial concentration: NaN
name: ppERK(cytosol)
boundary condition: true
is version of: REACT 3037
initial amount: NaN
in compartment: 143010

143189
value: 0.1
name: k4
type: LocalParameter

143211
constant: true
value: 3.07
name: tau1
type: Parameter

COPASI3
is: SBO:0000236
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 143010
name: x2
type: Species

143181
kinetic law: 027214
modifier: 027202
product: 027190
is version of: GO:0006397
fast: false
reversible: false
name: 5 cFOSm
type: Reaction

143179
kinetic law: 027178
modifier: 027165
modifier: 027153
product: 027141
is version of: GO:0009299
fast: false
reversible: false
name: 4 cFOSp
type: Reaction

143010
is version of: GO:0005623
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
name: compartment
type: Compartment

143207
constant: true
value: 0.06
name: k13
type: Parameter

143190
value: 0.15
name: k5
type: LocalParameter

COPASI2
is: SBO:0000236
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 143010
name: x1
type: Species

026995
stoichiometry: 1.0
species: COPASI3
type: SpeciesReference

COPASI8
is: SBO:0000252
boundary condition: false
has only substance units: false
is version of: REACT 21788.1
is version of: P01100
initial concentration: 0.0
initial amount: NaN
name: cFOS
in compartment: 143010
type: Species
constant: false

143197
value: 0.3
name: k9
type: LocalParameter

143208
constant: true
value: 1.0
name: L
type: Parameter

COPASI10
encodes: P01100
type: Species
in compartment: 143010
has only substance units: false
initial concentration: 0.0
initial amount: NaN
name: cFOSmRNA
encodes: REACT 21788.1
boundary condition: false
constant: false
is: SBO:0000250

143177
kinetic law: 027093
modifier: 027081
product: 027069
is version of: GO:0004707
fast: false
reversible: false
name: 2b DUSP
type: Reaction

026959
exponent: 1.0
scale: -3
multipler: 1.0
kind: MOLE
type: SBMLUnit

143213
constant: true
value: 472.0
name: tau
type: Parameter

COPASI9
initial amount: NaN
in compartment: 143010
boundary condition: false
type: Species
is version of: P01100
initial concentration: 0.0
constant: false
name: pc-FOS
is: SBO:0000252
has only substance units: false
is: REACT 21988.1

143183
product: 027288
modifier: 027312
kinetic law: 027324
reversible: false
is version of: REACT_21251
is version of: http://identifiers.org/ec-code/2.7.11.24
modifier: 027300
fast: false
name: 7 pcFOS
type: Reaction

143209
constant: true
value: 1.09
name: K1
type: Parameter

143212
constant: true
value: 2.89
name: K
type: Parameter

027226
stoichiometry: 1.0
species: COPASI8
type: SpeciesReference

143178
kinetic law: 027129
modifier: 027117
product: 027105
is version of: REACT_20562
is version of: REACT 20510.1
fast: false
reversible: false
name: 3 pRSKn
type: Reaction

143182
kinetic law: 027276
reversible: false
product: 027226
modifier: 027239
is version of: GO:0006412
type: Reaction
modifier: 027252
modifier: 027264
fast: false
name: 6 cFOS

026911
exponent: 1.0
scale: -3
multipler: 1.0
kind: LITRE
type: SBMLUnit