TY - JOUR
T1 - The Vav family
T2 - At the crossroads of signaling pathways
AU - Swat, Wojciech
AU - Fujikawa, Keiko
PY - 2005
Y1 - 2005
N2 - The Vav family of Rho-guanine nucleotide exchange factors (GEFs) is thought to control a diverse array of signaling pathways emanating from antigen receptors in lymphocytes, although the exact mechanism by which Vav exerts its function is only beginning to emerge. Vav proteins are modular and contain the Db1-homology domain, typical of all known Rho-GEFs, in addition to several other structural domains characteristic of proteins involved in signal transduction. Recently, our laboratory generated mice congenitally lacking all three Vav isoforms, providing genetic evidence that the Vav family is critical and nonredundant in T- and B-lymphocyte development and function and is essential in the formation of the adaptive immune system. These experiments also demonstrated that Vav proteins are indispensable for both T-cell receptor - and B-cell receptor-induced Ca++ fluxes. However, detailed analyses of Vav-deficient mice revealed unexpected complexity of Vav involvement in cellular activation. Notably, we observed lineage-specific Vav regulation of mitogen-activated protein kinase signaling, in which Vav was required in T-cells, but not in B-cells. Moreover, the three Vav proteins appear to function specifically in distinct signaling pathways emanating from activating receptors of natural killer cells that trigger natural cytotoxicity.
AB - The Vav family of Rho-guanine nucleotide exchange factors (GEFs) is thought to control a diverse array of signaling pathways emanating from antigen receptors in lymphocytes, although the exact mechanism by which Vav exerts its function is only beginning to emerge. Vav proteins are modular and contain the Db1-homology domain, typical of all known Rho-GEFs, in addition to several other structural domains characteristic of proteins involved in signal transduction. Recently, our laboratory generated mice congenitally lacking all three Vav isoforms, providing genetic evidence that the Vav family is critical and nonredundant in T- and B-lymphocyte development and function and is essential in the formation of the adaptive immune system. These experiments also demonstrated that Vav proteins are indispensable for both T-cell receptor - and B-cell receptor-induced Ca++ fluxes. However, detailed analyses of Vav-deficient mice revealed unexpected complexity of Vav involvement in cellular activation. Notably, we observed lineage-specific Vav regulation of mitogen-activated protein kinase signaling, in which Vav was required in T-cells, but not in B-cells. Moreover, the three Vav proteins appear to function specifically in distinct signaling pathways emanating from activating receptors of natural killer cells that trigger natural cytotoxicity.
KW - Antigen receptor
KW - Ca
KW - Lymphocyte
KW - Mitogen-activated protein kinase
KW - Natural killer cell
UR - http://www.scopus.com/inward/record.url?scp=23844538589&partnerID=8YFLogxK
U2 - 10.1385/IR:32:1-3:259
DO - 10.1385/IR:32:1-3:259
M3 - Review article
C2 - 16106078
AN - SCOPUS:23844538589
SN - 0257-277X
VL - 32
SP - 259
EP - 265
JO - Immunologic Research
JF - Immunologic Research
IS - 1-3
ER -