Research ArticleImmunology

Function of the Nucleotide Exchange Activity of Vav1 in T Cell Development and Activation

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Science Signaling  15 Dec 2009:
Vol. 2, Issue 101, pp. ra83
DOI: 10.1126/scisignal.2000420

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Not All GEF All The Time

Vav1 is a guanine nucleotide exchange factor (GEF) that activates members of the Rho family of small guanosine triphosphatases (GTPases). Vav1 is an important mediator of T cell receptor (TCR) signaling and is required for the development of T cells in the thymus and for their activation and proliferation in response to antigen stimulation. TCR-stimulated remodeling of the actin cytoskeleton also requires Vav1; however, whether all of these functions of Vav1 require its GEF activity is unknown. Saveliev et al. generated mice that expressed a mutant Vav1 lacking GEF activity but that otherwise retained the properties of wild-type Vav1. Although the GEF activity of Vav1 was required for positive selection of CD4 and CD8 single-positive thymocytes and for T cell activation, other TCR- and Vav1-dependent processes were unaffected by the loss of its GEF activity, such as Ca2+ flux and activation of extracellular signal–regulated kinase (ERK). The authors suggest that Vav1 might play a role as an adaptor protein to mediate its GEF-independent functions, particularly for the activation of PLC-γ1.