The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway

Cell Signal. 2008 Mar;20(3):453-9. doi: 10.1016/j.cellsig.2007.10.002. Epub 2007 Oct 11.


Shp2 is a ubiquitous tyrosine phosphatase containing Src Homology 2 domains which plays major biological functions in response to various growth factors, hormones or cytokines. This is essentially due to its particularity of promoting the activation of the Ras/Mitogen-activated protein kinase pathway. Recent progresses have been made in the understanding of the molecular mechanisms involved in this regulation. We review here, and discuss the physiological relevance, of the following molecular functions of Shp2 that have been proposed to couple the phosphatase to Ras activation: promoter of Grb2/Sos recruitment through direct binding to Grb2, binding partner and regulator of SHPS-1, negative regulator of Sprouty, negative regulator of RasGAP recruitment, and activator of Src through dephosphorylation of Src-regulatory proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Enzyme Activation
  • GRB2 Adaptor Protein / metabolism
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
  • Receptors, Immunologic / metabolism
  • Signal Transduction*
  • Vault Ribonucleoprotein Particles / metabolism
  • ras GTPase-Activating Proteins / metabolism
  • ras Proteins / metabolism*
  • src-Family Kinases / metabolism


  • GRB2 Adaptor Protein
  • Receptors, Immunologic
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • ras GTPase-Activating Proteins
  • src-Family Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • ras Proteins