Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes

Gina M. Doody, Daniel D. Billadeau, Elizabeth Clayton, Amanda Hutchings, Robert Berland, Simon McAdam, Paul J. Leibson, Martin Turner

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

We show here that Vav-2 is tyrosine phosphorylated following antigen receptor engagement in both B- and T-cells, but potentiates nuclear factor of activated T cells (NFAT)-dependent transcription only in B cells. Vav-2 function requires the N-terminus, as well as functional Dbl homology and SH2 domains. Moreover, the enhancement of NFAT-dependent transcription by Vav-2 can be inhibited by a number of dominant-negative GTPases. The ability of Vav-2 to potentiate NFAT-dependent transcription correlates with its ability to promote a sustained calcium flux. Thus, Vav-2 augments the calcium signal in B cells but not T cells, and a truncated form of Vav-2 can neither activate NFAT nor augment calcium signaling. The CD19 co-receptor physically interacts with Vav-2 and synergistically enhances Vav-2 phosphorylation induced by the B-cell receptor (BCR). In addition, we found that Vav-2 augments CD19-stimulated NFAT-dependent transcription, as well as transcription from the CD5 enhancer. These data suggest a role for Vav-2 in transducing BCR signals to the transcription factor NFAT and implicate Vav-2 in the integration of BCR and CD19 signaling.

Original languageEnglish (US)
Pages (from-to)6173-6184
Number of pages12
JournalEMBO Journal
Volume19
Issue number22
DOIs
StatePublished - Nov 15 2000

Keywords

  • CD 19
  • Lymphocyte
  • RhoG
  • Signaling
  • Vav

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Doody, G. M., Billadeau, D. D., Clayton, E., Hutchings, A., Berland, R., McAdam, S., Leibson, P. J., & Turner, M. (2000). Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes. EMBO Journal, 19(22), 6173-6184. https://doi.org/10.1093/emboj/19.22.6173