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Sci. Signal., 15 December 2009
Vol. 2, Issue 101, p. ra83
[DOI: 10.1126/scisignal.2000420]

RESEARCH ARTICLES

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

Alexander Saveliev1, Lesley Vanes1, Olga Ksionda1, Jonathan Rapley1,2, Stephen J. Smerdon2, Katrin Rittinger2, and Victor L. J. Tybulewicz1*

1 Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, UK.
2 Division of Molecular Structure, MRC National Institute for Medical Research, London NW7 1AA, UK.

Abstract: The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal–regulated kinase and protein kinase D1, and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions.

* To whom correspondence should be addressed. E-mail: vtybule{at}nimr.mrc.ac.uk

Citation: A. Saveliev, L. Vanes, O. Ksionda, J. Rapley, S. J. Smerdon, K. Rittinger, V. L. J. Tybulewicz, Function of the Nucleotide Exchange Activity of Vav1 in T Cell Development and Activation. Sci. Signal. 2, ra83 (2009).

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