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Publication : Function of the nucleotide exchange activity of vav1 in T cell development and activation.

First Author  Saveliev A Year  2009
Journal  Sci Signal Volume  2
Issue  101 Pages  ra83
PubMed ID  20009105 Mgi Jnum  J:190087
Mgi Id  MGI:5447945 Doi  10.1126/scisignal.2000420
Citation  Saveliev A, et al. (2009) Function of the nucleotide exchange activity of vav1 in T cell development and activation. Sci Signal 2(101):ra83
abstractText  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.
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