Guanine exchange-dependent and -independent effects of Vav1 on integrin-induced T cell spreading

Abstract : Vav1 is a 95-kDa member of the Dbl family of guanine exchange factors and a prominent hemopoietic cell-specific protein tyrosine kinase substrate, the involvement of which in cytoskeletal rearrangements has been linked to its ability to activate Rho family small GTPases. beta(1) integrin ligation by fibronectin induced Vav1 phosphorylation in peripheral blood lymphocytes and in two different T cell lines. Vav1 overexpression led to massive T cell spreading on beta(1) integrin ligands, and, conversely, two dominant negative mutants blocked integrin-induced spreading. Vav1 and beta(1) integrin ligation synergistically activated Pak, but not Rac, Cdc42, or c-Jun N-terminal kinase. In addition, Vav1 cooperated with constitutively active V12Rac mutant, but not with V12Cdc42, to induce T cell spreading after integrin occupancy. More importantly, a Vav1 mutant that lacked guanine exchange factor activity still cooperated with V12Rac. In contrast, a point mutation in the SH2 domain of Vav1 abolished this synergistic effect. Therefore, our results suggest a new regulatory effect of Vav1 in T cell spreading, which is independent of its guanine exchange factor activity.
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M. A. Schwartz, J. R. Hu, W. B. Kiosses, A. Altman, M. Villalba, et al.. Guanine exchange-dependent and -independent effects of Vav1 on integrin-induced T cell spreading. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2003, 170 (1), pp.41--47. ⟨hal-02239684⟩



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