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The vav family

At the crossroads of signaling pathways

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Abstract

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 Dbl-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 experimental also demonstrated that Vav proteins are indispensable for both T-cell receptor—and B-cell receptr-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-cell, 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.

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Author information

Author notes

  1. Keiko Fujikawa

    Present address: Department of Biochemistry, Hokkaido University Graduate School of Medicine, 060-8638, Sapporo, Japan

  2. Wojciech Swat PhD

    Present address: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8118, 63110, St. Louis

Authors and Affiliations

  1. Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8118, 63110, St. Louis

    Keiko Fujikawa

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  1. Wojciech Swat PhD
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Swat, W., Fujikawa, K. The vav family. Immunol Res 32, 259–265 (2005). https://doi.org/10.1385/IR:32:1-3:259

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