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Vav‐2 controls NFAT‐dependent transcription inB‐ but not T‐lymphocytes
Author(s) -
Doody Gina M.,
Billadeau Daniel D.,
Clayton Elizabeth,
Hutchings Amanda,
Berland Robert,
McAdam Simon,
Leibson Paul J.,
Turner Martin
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.22.6173
Subject(s) - nfat , library science , biology , genetics , computer science , transcription factor , gene
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. More over, 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.