BIOMD0000000031
type: SBMLModel
species: metaid_0000132
units def: metaid_0000038
parameter: metaid_0000019
parameter: metaid_0000025
species: metaid_0000032
parameter: metaid_0000024
parameter: metaid_0000021
is version of: GO:0000165
is described by: http://identifiers.org/pubmed/14744999
name: Markevich2004_MAPK_orderedMM2kinases
reaction: metaid_0000043
parameter: metaid_0000020
length unit: length
is: MODEL6618738800
parameter: metaid_0000023
created:
  W3 CDTF: Thu Jun 30 11:11:00 BST 2005
species: metaid_0000033
species: metaid_0000030
compartment: metaid_0000028
curated: true
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Nicolas
    family: Le Novère
occurs in: http://identifiers.org/taxonomy/8355
area units: area
notes: The model describes the double phosphorylation of MAP kinase by an ordered mechanism using the Michaelis-Menten formalism. Two different enzymes, MAPKK1 and MAPKK2, successively phosphorylate the MAP kinase, but one and the same phosphatase dephosphorylates both sites. The model reproduces figure S9 in the supplemental material of the article. The model is further described in: Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. Markevich NI, Hoek JB, Kholodenko BN. J Cell Biol. 2004 Feb 2;164(3):353-9. PMID: 14744999 ; DOI: 10.1083/jcb.200308060 Abstract: Mitogen-activated protein kinase (MAPK) cascades can operate as bistable switches residing in either of two different stable states. MAPK cascades are often embedded in positive feedback loops, which are considered to be a prerequisite for bistable behavior. Here we demonstrate that in the absence of any imposed feedback regulation, bistability and hysteresis can arise solely from a distributive kinetic mechanism of the two-site MAPK phosphorylation and dephosphorylation. Importantly, the reported kinetic properties of the kinase (MEK) and phosphatase (MKP3) of extracellular signal-regulated kinase (ERK) fulfill the essential requirements for generating a bistable switch at a single MAPK cascade level. Likewise, a cycle where multisite phosphorylations are performed by different kinases, but dephosphorylation reactions are catalyzed by the same phosphatase, can also exhibit bistability and hysteresis. Hence, bistability induced by multisite covalent modification may be a widespread mechanism of the control of protein activity. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 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 …
time units: metaid_0000017
reaction: metaid_0000046
substance units: metaid_0000038
species: metaid_0000031
species: metaid_0000029
parameter: metaid_0000027
parameter: metaid_0000026
reaction: metaid_0000045
volume units: metaid_0000323
parameter: metaid_0000022
modified:
  W3 CDTF: Tue May 15 22:43:41 BST 2012
reaction: metaid_0000044

metaid_0000132
type: Species
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constant: true
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 1.0
in compartment: metaid_0000028
name: MAPKK2

metaid_0000028
type: Compartment
constant: true
size: 1.0
spatial dimensions: 3.0

metaid_0000038
type: SBMLUnitsDef
unit: 079389
name: nanomole (default)

079389
type: SBMLUnit
exponent: 1.0
scale: -9
multipler: 1.0
kind: MOLE

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type: Parameter
constant: true
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metaid_0000025
type: Parameter
constant: true
value: 0.06

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is: Q05116
constant: true
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initial concentration: NaN
initial amount: 100.0
in compartment: metaid_0000028
name: MAPKK1

metaid_0000024
type: Parameter
constant: true
value: 5.0

metaid_0000021
type: Parameter
constant: true
value: 15.0

metaid_0000043
type: Reaction
is homolog to: REACT 136
name: phosphorylation of MAPK
is version of: http://identifiers.org/ec-code/2.7.12.2
is version of: GO:0004708
product: 079413
kinetic law: 079437
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reactant: 079401
reversible: false
is version of: GO:0006468
modifier: 079425

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constant: false
boundary condition: false
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initial concentration: NaN
initial amount: 500.0
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type: Parameter
constant: true
value: 50.0

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type: Parameter
constant: true
value: 0.084

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type: Species
is: Q90W58
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boundary condition: false
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initial concentration: NaN
initial amount: 100.0
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kinetic law: 079618
reactant: 079570
is version of: GO:0006470
is version of: http://identifiers.org/ec-code/3.1.3.16
reversible: false
name: dephosphorylation of P-MAPK
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fast: false
modifier: 079594
product: 079582

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constant: true
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type: Reaction
name: dephosphorylation of PP-MAPK
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type: Parameter
constant: true
value: 500.0

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type: Reaction
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name: phosphorylation of P-MAPK
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reversible: false
is version of: http://identifiers.org/ec-code/2.7.12.2
is version of: GO:0004708
modifier: 079485
is homolog to: REACT 136

079461
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