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type: SBMLModel
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parameter: metaid_0000019
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notes: The model corresponds to the schemas 1 and 2 of Markevich et al 2004, as described in the figure 1 and modelled using Michaelis-Menten like kinetics. Phosphorylations and dephosphorylations follow distributive ordered kinetics. It reproduces figure 3 in the main 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 A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Dat…
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is version of: GO:0000165
species: metaid_0000032
species: metaid_0000029
parameter: metaid_0000023
modified:
  W3 CDTF: Tue May 15 22:42:12 BST 2012
curated: true
name: Markevich2004_MAPK_orderedMM
is: MODEL6618496308
reaction: metaid_0000046
reaction: metaid_0000043
parameter: metaid_0000024
area units: area
parameter: metaid_0000027
substance units: metaid_0000038
reaction: metaid_0000045
length unit: length
parameter: metaid_0000026
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Nicolas
    family: Le Novère
is described by: http://identifiers.org/pubmed/14744999
parameter: metaid_0000025
parameter: metaid_0000020
occurs in: http://identifiers.org/taxonomy/8355
species: metaid_0000031
time units: metaid_0000017
created:
  W3 CDTF: Mon May 23 14:41:40 BST 2005
volume units: metaid_0000323

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value: 500.0

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name: phosphorylation of P-MAPK
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is version of: http://identifiers.org/ec-code/2.7.12.2
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