Activation of CD4 T cells by Raf-independent effectors of Ras

Proc Natl Acad Sci U S A. 2003 May 13;100(10):6003-8. doi: 10.1073/pnas.1031494100. Epub 2003 Apr 29.

Abstract

Small GTPase Ras is capable of mediating activation in T lymphocytes by using Raf kinase-dependent signaling pathway. Other effectors of Ras exist, however, suggesting that targets of Ras alternative to Raf may also contribute to T cell functions. Here we demonstrate that Ras(V12G37) mutant that fails to bind Raf, potently increases intracellular calcium concentration and cytokine production in primary antigen-stimulated T cells. From three known effectors which retain the ability to interact with Ras(V12G37), overexpression of phospholipase C epsilon but not that of RIN1 or Ral guanine nucleotide exchange factors enhanced cytokine and nuclear factor-activated T cell reporter T cell responses. Hence T cell activation can be critically regulated by the Ras effector pathway independent from Raf that can be mimicked by phospholipase C epsilon.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA Primers
  • Humans
  • Lymphocyte Activation*
  • Mice
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-raf / metabolism
  • Rats
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • Transcription, Genetic
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Type C Phospholipases / genetics
  • ras GTPase-Activating Proteins / immunology*

Substances

  • DNA Primers
  • ras GTPase-Activating Proteins
  • Proto-Oncogene Proteins c-raf
  • Type C Phospholipases