| Literature DB >> 11376343 |
K Tedford1, L Nitschke, I Girkontaite, A Charlesworth, G Chan, V Sakk, M Barbacid, K D Fischer.
Abstract
Vav-1 and Vav-2 are closely related Dbl-homology GTP exchange factors (GEFs) for Rho GTPases. Mutation of Vav-1 disrupts T cell development and T cell antigen receptor-induced activation, but has comparatively little effect on B cells. We found that combined deletion of both Vav-1 and Vav-2 in mice resulted in a marked reduction in mature B lymphocyte numbers. Vav-1(-/-)Vav-2(-/-) B cells were unresponsive to B cell antigen receptor (BCR)-driven proliferation in vitro and to thymus-independent antigen in vivo. BCR-stimulated intracellular calcium mobilization was greatly impaired in Vav-1(-/-)Vav-2(-/-) B cells. These findings establish a role for Vav-2 in BCR calcium signaling and reveal that the Vav family of GEFs is critical to B cell development and function.Entities:
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Year: 2001 PMID： 11376343 DOI： 10.1038/88756
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606