Model Identifier
BIOMD0000000029
Short description

The model corresponds to the schema 3 of Markevich et al 2004, as described in the figure 2 and the supplementary table S3, and modelled using Michaelis-Menten like kinetics. Phosphorylations follow distributive random kinetics, while dephosphorylations follow an ordered mechanism.

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2007 The BioModels Team.
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Format
SBML (L2V1)
Related Publication
  • Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. Click here to expand
  • Nick I Markevich, Jan B Hoek, Boris N Kholodenko
  • The Journal of cell biology , 2/ 2004 , Volume 164 , Issue 3 , pages: 353-359 , PubMed ID: 14744999
  • Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, 1020 Locust St., Philadelphia, PA 19107, USA.
  • 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.
Contributors
Submitter of the first revision: Nicolas Le Novère
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modeller: Nicolas Le Novère

Metadata information

is (2 statements)
BioModels Database BIOMD0000000029
BioModels Database MODEL6618620128

isDescribedBy (1 statement)
PubMed 14744999

hasTaxon (1 statement)
Taxonomy Xenopus laevis

isVersionOf (1 statement)
Gene Ontology MAPK cascade

hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated
Modelling approach(es)
ordinary differential equation model

Connected external resources

Visualisation of this model on Menelmacar platform