public model
Short description
Related Publication
  • Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades.
  • Markevich NI, Hoek JB, Kholodenko BN
  • The Journal of cell biology , 2/ 2004 , Volume 164 , pages: 353-359
  • 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.
Nicolas Le Novère

Metadata information

BioModels Database MODEL6618676537
BioModels Database BIOMD0000000030
PubMed 14744999
Taxonomy Xenopus laevis
Gene Ontology GO:0000165
Curation status
Name Description Size Actions

Model files

BIOMD0000000030_url.xml SBML L2V1 representation of Markevich2004_MAPK_AllRandomElementary 47.47 KB Preview | Download

Additional files

BIOMD0000000030.svg Auto-generated Reaction graph (SVG) 56.56 KB Preview | Download
BIOMD0000000030.m Auto-generated Octave file 11.08 KB Preview | Download
BIOMD0000000030.pdf Auto-generated PDF file 226.06 KB Preview | Download
BIOMD0000000030.png Auto-generated Reaction graph (PNG) 193.21 KB Preview | Download
BIOMD0000000030.xpp Auto-generated XPP file 7.75 KB Preview | Download
BIOMD0000000030_urn.xml Auto-generated SBML file with URNs 50.93 KB Preview | Download
BIOMD0000000030-biopax3.owl Auto-generated BioPAX (Level 3) 67.62 KB Preview | Download
BIOMD0000000030-biopax2.owl Auto-generated BioPAX (Level 2) 41.28 KB Preview | Download
BIOMD0000000030.vcml Auto-generated VCML file 71.85 KB Preview | Download
BIOMD0000000030.sci Auto-generated Scilab file 6.82 KB Preview | Download

  • Model originally submitted by : Nicolas Le Novère
  • Submitted: Sep 13, 2005 2:38:08 PM
  • Last Modified: May 15, 2012 10:43:15 PM
  • Version: 2 public model Download this version
    • Submitted on: May 15, 2012 10:43:15 PM
    • Submitted by: Nicolas Le Novère
    • With comment: Current version of Markevich2004_MAPK_AllRandomElementary
  • Version: 1 public model Download this version
    • Submitted on: Sep 13, 2005 2:38:08 PM
    • Submitted by: Nicolas Le Novère
    • With comment: Original import of Markevich2005_MAPK_AllRandomElementary