BIOMD0000000394
type: SBMLModel
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
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
species: 089600
substance units: 142808
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

089834
type: Species
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

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

090126
type: Reaction
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

089855
type: Species
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

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

184495
type: SpeciesReference
stoichiometry: 1.0
species: 089834

184519
type: SpeciesReference
stoichiometry: 1.0
species: 089874

089874
type: Species
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)

184507
type: SpeciesReference
stoichiometry: 1.0
species: 089894

089894
type: Species
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)

090168
type: Parameter
constant: true
value: 0.614

090161
type: Parameter
constant: true
value: 0.511

090162
type: Parameter
constant: true
value: 0.47

090202
type: Parameter
constant: true
value: 0.73

090203
type: Parameter
constant: true
value: 1.13

089794
type: Species
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

090197
type: Parameter
constant: true
value: 1.65

090187
type: Parameter
constant: true
value: 1.459

090192
type: Parameter
constant: true
value: 0.558

089639
type: Species
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
name: 14_minus_3_minus_3
initial concentration: NaN
has only substance units: false
boundary condition: false
initial amount: 5.0
in compartment: 089440

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

090182
type: Parameter
constant: true
value: 0.693

089619
type: Species
name: PP2A
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

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

089479
type: Species
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
is version of: P31749
initial concentration: NaN
name: Akt
constant: false

089580
type: Species
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
constant: false
is version of: P30086

184015
type: SpeciesReference
stoichiometry: 1.0
species: 089697

089697
type: Species
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
name: Raf_minus_1
initial amount: 0.0
is version of: P04049
in compartment: 089440
boundary condition: false
constant: false

184003
type: SpeciesReference
stoichiometry: 1.0
species: 089676

089676
type: Species
initial concentration: NaN
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

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

090212
type: Parameter
constant: true
value: 1.0

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

090207
type: Parameter
constant: true
value: 1.0

089459
type: Species
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
boundary condition: false
constant: false
initial concentration: NaN
name: Akt
in compartment: 089440

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

184111
type: SpeciesReference
stoichiometry: 1.0
species: 089519

089519
type: Species
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
boundary condition: false
in compartment: 089440
name: MEK1_minus_2

184099
type: SpeciesReference
stoichiometry: 1.0
species: 089501

089501
type: Species
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

090014
type: Reaction
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

184255
type: SpeciesReference
stoichiometry: 1.0
species: 089658

089658
type: Species
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

184243
type: SpeciesReference
stoichiometry: 1.0
species: 089559

089559
type: Species
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

090174
type: Parameter
constant: true
value: 1.219

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

184207
type: SpeciesReference
stoichiometry: 1.0
species: 089559

184195
type: SpeciesReference
stoichiometry: 1.0
species: 089541

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

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

184159
type: SpeciesReference
stoichiometry: 1.0
species: 089600

089600
type: Species
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
in compartment: 089440
name: RKIP

184147
type: SpeciesReference
stoichiometry: 1.0
species: 089580

090209
type: Parameter
constant: true
value: 1.0

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

184387
type: SpeciesReference
stoichiometry: 1.0
species: 089479

184375
type: SpeciesReference
stoichiometry: 1.0
species: 089459

090164
type: Parameter
constant: true
value: 0.786

090035
type: Reaction
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

184291
type: SpeciesReference
stoichiometry: 1.0
species: 089834

184279
type: SpeciesReference
stoichiometry: 2.0
species: 089737

089737
type: Species
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
notes: Long Name: EGFR Synonym: Gurken receptor, Erb, Neu, neuregulin Accession: P00542

090194
type: Parameter
constant: true
value: 0.725

090189
type: Parameter
constant: true
value: 1.021

090178
type: Parameter
constant: true
value: 2.0

090219
type: Parameter
constant: true
value: 1.0

090184
type: Parameter
constant: true
value: 0.787

090169
type: Parameter
constant: true
value: 0.636

090172
type: Parameter
constant: true
value: 1.367

090173
type: Parameter
constant: true
value: 0.583

090213
type: Parameter
constant: true
value: 1.0

090163
type: Parameter
constant: true
value: 1.083

090214
type: Parameter
constant: true
value: 1.0

090204
type: Parameter
constant: true
value: 1.0

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

184339
type: SpeciesReference
stoichiometry: 1.0
species: 089813

184327
type: SpeciesReference
stoichiometry: 1.0
species: 089813

090198
type: Parameter
constant: true
value: 2.0

090199
type: Parameter
constant: true
value: 0.074

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

184435
type: SpeciesReference
stoichiometry: 1.0
species: 089776

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

184459
type: SpeciesReference
stoichiometry: 1.0
species: 089794

184447
type: SpeciesReference
stoichiometry: 1.0
species: 089755

184423
type: SpeciesReference
stoichiometry: 1.0
species: 089755

090193
type: Parameter
constant: true
value: 0.038

090183
type: Parameter
constant: true
value: 0.463

090179
type: Parameter
constant: true
value: 0.626

090188
type: Parameter
constant: true
value: 0.566

090222
type: Parameter
constant: true
value: 1.0

090217
type: Parameter
constant: true
value: 1.0

090177
type: Parameter
constant: true
value: 0.293

090167
type: Parameter
constant: true
value: 0.727

090218
type: Parameter
constant: true
value: 1.0

090208
type: Parameter
constant: true
value: 1.0

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

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

ORG:
  orgname: EMBL-EBI
n:
  given: Vijayalakshmi
  family: Chelliah

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