BIOMD0000000028
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modified:
  W3 CDTF: Tue May 15 22:42:30 BST 2012
is version of: GO:0000165
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length unit: length
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is described by: http://identifiers.org/pubmed/14744999
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occurs in: http://identifiers.org/taxonomy/8355
name: Markevich2004_MAPK_phosphoRandomElementary
parameter: metaid_0000038
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substance units: metaid_0000003
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units def: metaid_0000003
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type: SBMLModel
notes: The model corresponds to the schema 3 of Markevich et al 2004, as described in the figure 2 and the supplementary table S2. Phosphorylations follow distributive random kinetics, while dephosphorylations follow an ordered mechanism. The phosphorylations are modeled with three elementary reactions: E+S<=>ES->E+P The dephosphorylations are modeled with five elementary reactions: E+S<=>ES->EP<=>E+P The model reproduces figure 5 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 Da…
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creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Nicolas
    family: Le Novère
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created:
  W3 CDTF: Mon May 23 17:11:24 BST 2005
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