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

59 Citations (Scopus)

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
StatePublished - Nov 15 2000

Fingerprint

NFATC Transcription Factors
T-cells
Transcription
B-Lymphocytes
T-Lymphocytes
Cells
Calcium
Antigen Receptors
Phosphorylation
Calcium Signaling
src Homology Domains
GTP Phosphohydrolases
Tyrosine
Transcription Factors
Fluxes

Keywords

  • CD 19
  • Lymphocyte
  • RhoG
  • Signaling
  • Vav

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Doody, G. M., Billadeau, D. D., Clayton, E., Hutchings, A., Berland, R., McAdam, S., ... Turner, M. (2000). Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes. EMBO Journal, 19(22), 6173-6184.

Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes. / Doody, Gina M.; Billadeau, Daniel D; Clayton, Elizabeth; Hutchings, Amanda; Berland, Robert; McAdam, Simon; Leibson, Paul J.; Turner, Martin.

In: EMBO Journal, Vol. 19, No. 22, 15.11.2000, p. 6173-6184.

Research output: Contribution to journalArticle

Doody, GM, Billadeau, DD, Clayton, E, Hutchings, A, Berland, R, McAdam, S, Leibson, PJ & Turner, M 2000, 'Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes', EMBO Journal, vol. 19, no. 22, pp. 6173-6184.
Doody GM, Billadeau DD, Clayton E, Hutchings A, Berland R, McAdam S et al. Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes. EMBO Journal. 2000 Nov 15;19(22):6173-6184.
Doody, Gina M. ; Billadeau, Daniel D ; Clayton, Elizabeth ; Hutchings, Amanda ; Berland, Robert ; McAdam, Simon ; Leibson, Paul J. ; Turner, Martin. / Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes. In: EMBO Journal. 2000 ; Vol. 19, No. 22. pp. 6173-6184.
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