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

We show here that Vav-2 is tyrosine phosphorylated following antigen recept or engagement in both B- and T-cells, but potentiates nuclear factor of act ivated T cells (NFAT)-dependent transcription only in B cells, Vav-2 functi on requires the N-terminus, as well as functional Dbl homology and SH2 doma ins. 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 activ ate NFAT nor augment calcium signaling. The CD19 co-receptor physically int eracts with Vav-2 and synergistically enhances Vav-2 phosphorylation induce d by the B-cell receptor (BCR), In addition, we found that Vav-2 augments C D19-stimulated NFAT-dependent transcription, as well as transcription from the CD5 enhancer. These data suggest a role for Vav-2 in transducing BCR si gnals to the transcription factor NFAT and implicate Vav-2 in the integrati on of BCR and CD19 signaling.