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191878
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metaid_0000106
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190953
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metaid_0000009
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191446
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191158
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191374
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metaid_0000027
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metaid_0000037
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type: Parameter

metaid_0000101
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metaid_0000057
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value: 15.0
type: Parameter

metaid_0000007
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value: 0.267
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metaid_0000077
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name: Rasa
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metaid_0000121
kinetic law: 192022
reactant: 191986
product: 191998
reversible: false
is: GO:0004707
type: Reaction
name: ERK mediated GSK3beta phosphorylation
is: GO:0016310
is: http://identifiers.org/ec-code/2.7.11.24
modifier: 192010
fast: false

metaid_0000111
type: Reaction
modifier: 191590
reversible: false
name: MEK activation
is version of: GO:0000186
reactant: 191566
is: http://identifiers.org/ec-code/2.7.11.1
fast: false
kinetic law: 191602
product: 191578
is version of: GO:0004709

metaid_0000017
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value: 0.417
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191278
stoichiometry: 1.0
species: metaid_0000072
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191818
stoichiometry: 1.0
species: metaid_0000084
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metaid_0000026
constant: true
value: 1200.0
type: Parameter

metaid_0000096
kinetic law: 191014
product: 191001
reactant: 190989
reactant: 190977
is version of: GO:0005515
fast: false
reversible: true
name: Axin/APC complex formation
type: Reaction

metaid_0000102
kinetic law: 191218
reactant: 191206
is version of: GO:0030163
fast: false
reversible: false
name: Unphosphorylated bCatenin degradation
type: Reaction

metaid_0000056
constant: true
value: 1.5
type: Parameter

metaid_0000036
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value: 1.5
type: Parameter

192070
persistant: true
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type: Trigger

metaid_0000016
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value: 206.0
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metaid_0000076
is version of: P62070
constant: false
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initial amount: NaN
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name: Rasi
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metaid_0000006
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type: Parameter

190857
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metaid_0000122
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metaid_0000097
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metaid_0000112
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metaid_0000039
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metaid_0000025
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191578
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192046
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notes: The two events are used to increase the value of wnt from 0 to 1 between time t=500minutes and t=1000minutes.
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191950
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191122
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191350
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191494
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metaid_0000052
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191182
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BIOMD0000000149
notes: Kim2007 - Crosstalk between Wnt and ERK pathways Experimental studies have shown that both Wnt and the MAPK pathways are involved in the pathogenesis of various kinds of cancers (eg. colorectal cancer). The crosstalk between the two pathways have also been identified. Here, Kim et al., (2007) have integrated the experimental evidences on crosstalk mechanisms between the two pathways into a pathway model, and have identified the existence of a hidden positive feedback loop and suggest that this positive feedback loop might participate in the pathogenesis of colorectal cancer. This model is described in the article: A hidden oncogenic positive feedback loop caused by crosstalk between Wnt and ERK pathways. Kim D, Rath O, Kolch W, Cho KH. Oncogene 2007 Jul; 26(31): 4571-4579 Abstract: The Wnt and the extracellular signal regulated-kinase (ERK) pathways are both involved in the pathogenesis of various kinds of cancers. Recently, the existence of crosstalk between Wnt and ERK pathways was reported. Gathering all reported results, we have discovered a positive feedback loop embedded in the crosstalk between the Wnt and ERK pathways. We have developed a plausible model that represents the role of this hidden positive feedback loop in the Wnt/ERK pathway crosstalk based on the integration of experimental reports and employing established basic mathematical models of each pathway. Our analysis shows that the positive feedback loop can generate bistability in both the Wnt and ERK signaling pathways, and this prediction was further validated by experiments. In particular, using the commonly accepted assumption that mutations in signaling proteins contribute to cancerogenesis, we have found two conditions through which mutations could evoke an irreversible response leading to a sustained activation of both pathways. One condition is enhanced production of beta-catenin, the other is a reduction of the velocity of MAP kinase phosphatase(s). This enables that high activities of Wn…
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type: Reaction

metaid_0000126
unit: 190700
name: nanomole
type: SBMLUnitsDef

191326
stoichiometry: 1.0
species: metaid_0000074
type: SpeciesReference

192094
persistant: true
initial value: true
type: Trigger

metaid_0000051
constant: true
value: 2.0
type: Parameter

metaid_0000012
constant: true
value: 50.0
type: Parameter

191410
stoichiometry: 1.0
species: metaid_0000077
type: SpeciesReference

metaid_0000029
constant: true
value: 9.0
type: Parameter

metaid_0000055
constant: true
value: 15.0
type: Parameter

metaid_0000065
is version of: P49841
constant: false
boundary condition: false
has only substance units: false
initial concentration: 49.1372
initial amount: NaN
in compartment: metaid_0000060
name: GSK3beta
type: Species

metaid_0000093
kinetic law: 190881
product: 190869
reactant: 190857
is: http://identifiers.org/ec-code/2.7.11.26
is version of: GO:0004674
fast: false
reversible: false
name: Activation of GSK/Axin/APC complex
type: Reaction

191110
stoichiometry: 1.0
species: metaid_0000069
type: SpeciesReference

191914
stoichiometry: 1.0
species: metaid_0000087
type: SpeciesReference

190809
stoichiometry: 1.0
species: metaid_0000066
type: SpeciesReference

metaid_0000113
fast: false
is version of: GO:0000187
type: Reaction
name: ERK activation
product: 191662
reactant: 191650
modifier: 191674
is: http://identifiers.org/ec-code/2.7.12.2
reversible: false
kinetic law: 191686
is version of: GO:0004708

metaid_0000127
unit: 190712
name: minute
type: SBMLUnitsDef

190736
stoichiometry: 1.0
species: metaid_0000062
type: SpeciesReference

191734
stoichiometry: 1.0
species: metaid_0000084
type: SpeciesReference

metaid_0000015
constant: true
value: 206.0
type: Parameter

metaid_0000100
kinetic law: 191170
reactant: 191158
is version of: GO:0030163
fast: false
reversible: false
name: Phosphorylated bCatenin degradation
type: Reaction

metaid_0000054
constant: true
value: 1.5
type: Parameter

metaid_0000028
constant: true
value: 10.0
type: Parameter

190821
stoichiometry: 1.0
species: metaid_0000065
type: SpeciesReference

metaid_0000094
kinetic law: 190917
product: 190905
reactant: 190893
is version of: GO:0016311
fast: false
reversible: false
name: Inactivation of GSK/Axin/APC complex
type: Reaction

metaid_0000064
has part: O15169
constant: false
initial concentration: 0.0076
boundary condition: false
in compartment: metaid_0000060
initial amount: NaN
has part: P49841
has only substance units: false
is: GO:0030877
name: APC/Axin/GSK3beta
has part: O95996
type: Species

metaid_0000128
is: GO:0005634
constant: true
size: 1.0
spatial dimensions: 3.0
name: nucleus
type: Compartment

191314
stoichiometry: 1.0
species: metaid_0000071
type: SpeciesReference

metaid_0000114
kinetic law: 191722
product: 191710
reactant: 191698
is version of: GO:0000188
fast: false
reversible: false
name: ERK inactivation
type: Reaction

191038
stoichiometry: 1.0
species: metaid_0000063
type: SpeciesReference

metaid_0000063
in compartment: metaid_0000060
constant: false
name: APC_ast/Axin_ast/GSK3beta
has part: P49841
initial concentration: 0.0153
is: GO:0030877
has part: O15169
type: Species
has part: O95996
initial amount: NaN
boundary condition: false
has only substance units: false

metaid_0000014
constant: true
value: 120.0
type: Parameter

orgname: California Institute of Technology

orgname: EMBL-EBI

given: Harish
family: Dharuri

W3 CDTF: Tue Jul 10 14:55:45 BST 2007

W3 CDTF: Fri Aug 02 18:33:39 BST 2013

n:
  given: Vijayalakshmi
  family: Chelliah