089600
constant: false
is version of: P30086
initial concentration: NaN
has only substance units: false
initial amount: 0.0
notes: Long Name: Raf-1 kinase inhibitor protein Synonym: Hippocampal cholinergic stimulatory peptide precursor,PEBP,Phosphatidylethanolamine-binding protein,Terminal flower 1,neuropolypeptide h3,prostastic binding protein Accession: P00548
boundary condition: false
type: Species
in compartment: 089440
name: RKIP

090198
constant: true
value: 2.0
type: Parameter

184111
stoichiometry: 1.0
species: 089519
type: SpeciesReference

184279
stoichiometry: 2.0
species: 089737
type: SpeciesReference

089459
has only substance units: false
notes: Long Name: Thymoma viral proto-oncogene Synonym: PKB,RAC protein kinase,protein kinase B Accession: P00551
initial amount: 5.0
is version of: P31749
type: Species
boundary condition: false
constant: false
initial concentration: NaN
name: Akt
in compartment: 089440

089943
kinetic law: 184135
modifier: 184123
product: 184111
reactant: 184099
notes: kinetics of non-modulated unireactant enzymes
fast: false
reversible: true
type: Reaction

090184
constant: true
value: 0.787
type: Parameter

089913
modifier: 184063
modifier: 184027
modifier: 184075
modifier: 184039
fast: false
type: Reaction
product: 184015
notes: kinetics of unireactant enzymes
reactant: 184003
kinetic law: 184087
reversible: true
modifier: 184051

090167
constant: true
value: 0.727
type: Parameter

090177
constant: true
value: 0.293
type: Parameter

089676
initial concentration: NaN
type: Species
initial amount: 5.0
boundary condition: false
constant: false
has only substance units: false
in compartment: 089440
notes: Long Name: RAF proto-oncogene serine/threonine-protein kinase Synonym: C-Raf,MAP kinase kinase kinase,Raf-1 Accession: P00560
name: Raf_minus_1
is version of: P04049

184507
stoichiometry: 1.0
species: 089894
type: SpeciesReference

184159
stoichiometry: 1.0
species: 089600
type: SpeciesReference

184375
stoichiometry: 1.0
species: 089459
type: SpeciesReference

090199
constant: true
value: 0.074
type: Parameter

184423
stoichiometry: 1.0
species: 089755
type: SpeciesReference

089501
in compartment: 089440
notes: Long Name: MAP/ERK kinase Synonym: Dual specificity mitogen-activated protein kinase kinase Accession: P00559
initial amount: 5.0
initial concentration: NaN
is version of: Q02750
has only substance units: false
constant: false
boundary condition: false
name: MEK1_minus_2
type: Species

090202
constant: true
value: 0.73
type: Parameter

089439
constant: true
size: 1.0
spatial dimensions: 3.0
type: Compartment

089991
kinetic law: 184231
modifier: 184219
product: 184207
reactant: 184195
notes: kinetics of non-modulated unireactant enzymes
fast: false
reversible: true
type: Reaction

090104
fast: false
modifier: 184471
reactant: 184435
product: 184459
kinetic law: 184483
type: Reaction
product: 184447
notes: reversible rapid-equilibrium random order ternary-complex mechanism with two products
reversible: true
reactant: 184423

090209
constant: true
value: 1.0
type: Parameter

184195
stoichiometry: 1.0
species: 089541
type: SpeciesReference

090179
constant: true
value: 0.626
type: Parameter

090203
constant: true
value: 1.13
type: Parameter

089718
type: Species
notes: Long Name: Epidermal growth factor Synonym: gurken,transforming growth factor alpha Accession: P00549
initial concentration: NaN
name: EGF
in compartment: 089439
initial amount: 5.0
constant: false
boundary condition: false
has only substance units: false
is version of: P01133

089794
notes: Long Name: GTP Synonym: Synonym not specified Accession: S01653
name: GTP
has only substance units: false
in compartment: 089440
boundary condition: false
initial concentration: NaN
initial amount: 0.0
constant: false
is: CHEBI:15996
type: Species

089894
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 089440
name: Complex(Grb2/../PLC)
type: Species

089580
notes: Long Name: Raf-1 kinase inhibitor protein Synonym: Hippocampal cholinergic stimulatory peptide precursor,PEBP,Phosphatidylethanolamine-binding protein,Terminal flower 1,neuropolypeptide h3,prostastic binding protein Accession: P00548
in compartment: 089440
name: RKIP
initial amount: 5.0
initial concentration: NaN
boundary condition: false
has only substance units: false
type: Species
constant: false
is version of: P30086

090213
constant: true
value: 1.0
type: Parameter

089855
is version of: CHEBI:114785
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.5
in compartment: 089439
name: erlotinib
type: Species

089541
is version of: GO:0004707
notes: Long Name: Extracellular signal-regulated kinase Synonym: MAPK,Mitogen-activated protein kinase,pp42/44 Accession: P00543
type: Species
has only substance units: false
name: ERK1_minus_2
initial concentration: NaN
initial amount: 5.0
constant: false
in compartment: 089440
boundary condition: false

090204
constant: true
value: 1.0
type: Parameter

090197
constant: true
value: 1.65
type: Parameter

090014
kinetic law: 184267
product: 184255
reactant: 184243
notes: mass action rate law for first order forward, first order reverse, reversible reactions, continuous scheme
fast: false
reversible: true
type: Reaction

184291
stoichiometry: 1.0
species: 089834
type: SpeciesReference

089440
constant: true
size: 1.0
spatial dimensions: 3.0
name: Cytosol
type: Compartment

184435
stoichiometry: 1.0
species: 089776
type: SpeciesReference

090214
constant: true
value: 1.0
type: Parameter

184387
stoichiometry: 1.0
species: 089479
type: SpeciesReference

184099
stoichiometry: 1.0
species: 089501
type: SpeciesReference

090187
constant: true
value: 1.459
type: Parameter

090164
constant: true
value: 0.786
type: Parameter

089874
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 089440
name: Complex_br_(EGFR/../_br_GAP)
type: Species

090126
reversible: false
notes: mass action rate law for second order irreversible reactions, two reactants, continuous scheme
modifier: 184531
kinetic law: 184543
reactant: 184495
product: 184519
reactant: 184507
fast: false
type: Reaction

184339
stoichiometry: 1.0
species: 089813
type: SpeciesReference

BIOMD0000000394
species: 089834
reaction: 090126
parameter: 090168
species: 089855
notes: This model is from the article: A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways. Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S. OMICS 2011 Oct;15(10):729-37. 21978399 , Abstract: The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to in fluence cell fate specification in the developing nervous system. Here we attempt ed to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Ou r model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E (spl)] genes and enhancement of Shh target genes by a SAG agonist that were effec tively demonstrated computationally and were consistent with experimental studies . However, in the case of model simulation of Wnt and EGF pathways, the model net work did not supply any concurrent results with experimental data despite the fac t that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species conne cted by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted th e regulation of a single target gene, Hes-1, based on drug-induced simulations. T hese simulations provided results that matched with experimental studies. Therefo re, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferati on, and differentiation during mammalian central nervous system development. To o ur knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores t he flow of positive and negative regulatory signals modulated by drugs. Note: EGFR belongs to the human epiderm…
parameter: 090161
species: 089894
parameter: 090162
parameter: 090202
parameter: 090203
species: 089794
parameter: 090197
parameter: 090187
parameter: 090192
is: MODEL1101270003
species: 089639
species: 089813
parameter: 090182
species: 089619
type: SBMLModel
reaction: 089913
area units: 498119
parameter: 090212
species: 089718
name: Sivakumar2011_EGFReceptorSignalingPathway
compartment: 089440
parameter: 090207
occurs in: CL:0000047
species: 089580
species: 089874
is described by: http://identifiers.org/pubmed/21978399
species: 089459
reaction: 089943
species: 089479
reaction: 090014
parameter: 090174
is version of: GO:0007173
occurs in: http://identifiers.org/taxonomy/40674
species: 089676
reaction: 089991
reaction: 089968
species: 089658
substance units: 142808
species: 089600
parameter: 090209
reaction: 090081
parameter: 090164
species: 089501
reaction: 090035
parameter: 090194
parameter: 090189
species: 089559
parameter: 090178
parameter: 090219
curated: true
parameter: 090184
parameter: 090169
time units: 949038
parameter: 090172
parameter: 090173
parameter: 090213
parameter: 090163
parameter: 090214
parameter: 090204
reaction: 090058
parameter: 090198
parameter: 090199
volume units: 142784
species: 089519
reaction: 090104
species: 089755
species: 089737
species: 089697
species: 089776
parameter: 090193
parameter: 090183
parameter: 090179
parameter: 090188
length unit: length
species: 089541

090178
constant: true
value: 2.0
type: Parameter

089834
name: EGFR
boundary condition: false
has only substance units: false
notes: Long Name: EGFR Synonym: Gurken receptor, Erb, Neu, neuregulin Accession: P00542
in compartment: 089440
constant: false
initial amount: 0.0
initial concentration: NaN
is version of: Q504U8
type: Species

089639
constant: false
is version of: P61981
notes: Long Name: 14-3-3 Synonym: PAR-5,Stratifin,protein kinase C inhibitor protein-1 (KCIP-1) Accession: P00539
type: Species
name: 14_minus_3_minus_3
initial concentration: NaN
has only substance units: false
boundary condition: false
initial amount: 5.0
in compartment: 089440

090188
constant: true
value: 0.566
type: Parameter

090081
kinetic law: 184411
modifier: 184399
product: 184387
reactant: 184375
notes: kinetics of non-modulated unireactant enzymes
fast: false
reversible: true
type: Reaction

090219
constant: true
value: 1.0
type: Parameter

184003
stoichiometry: 1.0
species: 089676
type: SpeciesReference

090035
kinetic law: 184315
modifier: 184303
product: 184291
reactant: 184279
notes: reversible rapid-equilibrium random order ternary-complex mechanism with one product
fast: false
reversible: true
type: Reaction

089619
name: PP2A
type: Species
notes: Long Name: protein phosphatase 2A Synonym: Serine/threonine protein phosphatase 2A Accession: P00547
has part: P62714
boundary condition: false
in compartment: 089440
initial concentration: NaN
has only substance units: false
initial amount: 5.0
constant: false

184447
stoichiometry: 1.0
species: 089755
type: SpeciesReference

090173
constant: true
value: 0.583
type: Parameter

090168
constant: true
value: 0.614
type: Parameter

090163
constant: true
value: 1.083
type: Parameter

090194
constant: true
value: 0.725
type: Parameter

184495
stoichiometry: 1.0
species: 089834
type: SpeciesReference

090189
constant: true
value: 1.021
type: Parameter

184207
stoichiometry: 1.0
species: 089559
type: SpeciesReference

184327
stoichiometry: 1.0
species: 089813
type: SpeciesReference

090212
constant: true
value: 1.0
type: Parameter

090172
constant: true
value: 1.367
type: Parameter

089737
has only substance units: false
name: EGFR
initial concentration: NaN
in compartment: 089440
constant: false
is version of: Q504U8
initial amount: 5.0
boundary condition: false
type: Species
notes: Long Name: EGFR Synonym: Gurken receptor, Erb, Neu, neuregulin Accession: P00542

184255
stoichiometry: 1.0
species: 089658
type: SpeciesReference

090162
constant: true
value: 0.47
type: Parameter

089658
notes: Long Name: Mitogenesis Differentiation Synonym: Synonym not specified Accession: U02228
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 1.0
in compartment: 089440
name: Mitogenesis_br_Differentiation
type: Species

089519
notes: Long Name: MAP/ERK kinase Synonym: Dual specificity mitogen-activated protein kinase kinase Accession: P00559
is version of: Q02750
constant: false
initial concentration: NaN
has only substance units: false
initial amount: 0.0
type: Species
boundary condition: false
in compartment: 089440
name: MEK1_minus_2

089968
kinetic law: 184183
modifier: 184171
product: 184159
reactant: 184147
notes: kinetics of non-modulated unireactant enzymes
fast: false
reversible: true
type: Reaction

090169
constant: true
value: 0.636
type: Parameter

090217
constant: true
value: 1.0
type: Parameter

089697
has only substance units: false
notes: Long Name: RAF proto-oncogene serine/threonine-protein kinase Synonym: C-Raf,MAP kinase kinase kinase,Raf-1 Accession: P00560
initial concentration: NaN
type: Species
name: Raf_minus_1
initial amount: 0.0
is version of: P04049
in compartment: 089440
boundary condition: false
constant: false

184015
stoichiometry: 1.0
species: 089697
type: SpeciesReference

089813
boundary condition: false
name: PKC
initial amount: 2.0
in compartment: 089440
type: Species
constant: false
initial concentration: NaN
has only substance units: false
is version of: P17252
notes: Long Name: PKC Synonym: Synonym not specified Accession: P00565

090207
constant: true
value: 1.0
type: Parameter

090192
constant: true
value: 0.558
type: Parameter

090182
constant: true
value: 0.693
type: Parameter

089559
name: ERK1_minus_2
boundary condition: false
initial concentration: NaN
notes: Long Name: Extracellular signal-regulated kinase Synonym: MAPK,Mitogen-activated protein kinase,pp42/44 Accession: P00543
has only substance units: false
initial amount: 0.0
constant: false
in compartment: 089440
is version of: GO:0004707
type: Species

090161
constant: true
value: 0.511
type: Parameter

184459
stoichiometry: 1.0
species: 089794
type: SpeciesReference

090218
constant: true
value: 1.0
type: Parameter

089776
name: GDP
notes: Long Name: GDP Synonym: Synonym not specified Accession: S01652
constant: false
initial concentration: NaN
has only substance units: false
type: Species
is: CHEBI:17552
in compartment: 089440
initial amount: 0.5
boundary condition: false

090208
constant: true
value: 1.0
type: Parameter

089755
is homolog to: P08646
boundary condition: false
notes: Long Name: Ras Synonym: Synonym not specified Accession: P00552
type: Species
initial amount: 5.0
initial concentration: NaN
constant: false
in compartment: 089440
name: Ras
has only substance units: false

090222
constant: true
value: 1.0
type: Parameter

184243
stoichiometry: 1.0
species: 089559
type: SpeciesReference

090183
constant: true
value: 0.463
type: Parameter

090174
constant: true
value: 1.219
type: Parameter

090058
kinetic law: 184363
modifier: 184351
product: 184339
reactant: 184327
notes: kinetics of non-modulated unireactant enzymes
fast: false
reversible: true
type: Reaction

090193
constant: true
value: 0.038
type: Parameter

184519
stoichiometry: 1.0
species: 089874
type: SpeciesReference

089479
initial amount: 0.0
notes: Long Name: Thymoma viral proto-oncogene Synonym: PKB,RAC protein kinase,protein kinase B Accession: P00551
boundary condition: false
has only substance units: false
in compartment: 089440
type: Species
is version of: P31749
initial concentration: NaN
name: Akt
constant: false

184147
stoichiometry: 1.0
species: 089580
type: SpeciesReference

ORG:
  orgname: Rajiv Gandhi Centre for Biotechnology
n:
  given: KC
  family: Sivakumar

orgname: EMBL-EBI

W3 CDTF: Fri Apr 20 20:40:21 BST 2012

given: Vijayalakshmi
family: Chelliah

W3 CDTF: Wed Nov 02 14:44:52 GMT 2011