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

被引:38
作者
del Pozo, MA
Schwartz, MA
Hu, JR
Kiosses, WB
Altman, A
Villalba, M
机构
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[2] La Jolla Inst Allergy & Immunol, Div Cell Biol, San Diego, CA 92121 USA
[3] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
[4] Fdn Ctr Nacl Invest Cardiovasc Carlos III, Madrid, Spain
[5] CNRS, Inst Genet Mol Montpellier, UMR 5535, Inst Federat Rech 24, Montpellier, France
[6] Univ Virginia, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA
关键词
D O I
10.4049/jimmunol.170.1.41
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页码:41 / 47
页数:7
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