Differential Regulation of TCR-mediated Gene Transcription by Vav Family Members

Shaheen Zakaria, Timothy S. Gomez, Doris N. Savoy, Simon McAdam, Martin Turner, Robert T. Abraham, Daniel D. Billadeau

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Although all three Vav family members are expressed in T lymphocytes, the role that Vav3 plays in T cell activation is poorly defined. Here we show that, like Vavl, Vav3 undergoes rapid tyrosine phosphorylation after T cell receptor (TCR) cross-linkage and interacts with the adaptor molecules SLP76 and 3BP2 in a SH2-dependent manner. However, depletion of Vav1 but not Vav3 protein by RNA interference affects TCR-mediated IL-2 promoter activity. In contrast, Vav3 function is specifically required for coupling TCR stimulation to serum response element-mediated gene transcription. These data indicate that, although both Vav proteins are biochemically coupled to the TCR, they regulate distinct molecular pathways leading to defined gene transcriptional events.

Original languageEnglish (US)
Pages (from-to)429-434
Number of pages6
JournalJournal of Experimental Medicine
Volume199
Issue number3
DOIs
StatePublished - Feb 2 2004

Keywords

  • GEF
  • SRE
  • Signal transduction
  • T cell
  • Vav

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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