Ras and extracellular signal-regulated kinase signaling in thymocytes and T cells

Trends Immunol. 2013 Jun;34(6):259-68. doi: 10.1016/j.it.2013.02.004. Epub 2013 Mar 15.


Extracellular signal-regulated kinase (ERK) activation is important for both thymocyte development and T cell function. Classically, signal transduction from the T cell antigen receptor (TCR) to ERK is thought to be regulated by signaling from Ras guanine nucleotide exchange factors (GEFs), through the small G protein Ras, to the three-tiered Raf-MAPK/ERK kinase (MEK)-ERK kinase cascade. Developing and mature T cells express four members of two RasGEF families, RasGRP1, RasGRP4, son of sevenless 1 (Sos1), and Sos2, and several models describing combined signaling from these RasGEFs have been proposed. However, recent studies suggest that existing models need revision to include both distinct and overlapping roles of multiple RasGEFs during thymocyte development and novel, Ras-independent signals to ERK that have been identified in peripheral T cells.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • MAP Kinase Signaling System / immunology
  • Receptor Cross-Talk
  • Receptors, Antigen, T-Cell / immunology*
  • SOS1 Protein / metabolism
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology*
  • ras Guanine Nucleotide Exchange Factors / metabolism
  • ras Proteins / metabolism*


  • Receptors, Antigen, T-Cell
  • SOS1 Protein
  • ras Guanine Nucleotide Exchange Factors
  • Extracellular Signal-Regulated MAP Kinases
  • ras Proteins