Signal-Transducing Adaptor Protein-2 Regulates Stromal Cell-Derived Factor-1α-Induced Chemotaxis in T Cells

被引:31
作者
Sekine, Yuichi
Ikeda, Osamu
Tsuji, Satoshi
Yamamoto, Chikako
Muromoto, Ryuta
Nanbo, Asuka
Oritani, Kenji [2 ]
Yoshimura, Akihiko [3 ]
Matsuda, Tadashi [1 ]
机构
[1] Hokkaido Univ, Dept Immunol, Grad Sch Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, Japan
[2] Osaka Univ, Dept Hematol & Oncol, Grad Sch Med, Osaka, Japan
[3] Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjuku Ku, Tokyo, Japan
关键词
LYMPHOCYTE CHEMOATTRACTANT; ACTIVATION; ADHESION; CHEMOKINES; KINASE; RAC; RHO; RECEPTOR; GTPASES; CXCR4;
D O I
10.4049/jimmunol.0902096
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin and Src homology 2-like domains, as well as a YXXQ motif in its C-terminal region. Our previous studies revealed that STAP-2 regulates integrin-mediated T cell adhesion. In the present study, we find that STAP-2 expression affects Jurkat T cell migration after stromal cell-derived factor-1 alpha (SDF-1 alpha)-treatment. Furthermore, STAP-2-deficient T cells exhibit reduced cell migration after SDF-1 alpha-treatment. Importantly, overexpression of STAP-2 in Jurkat T cells induces activation of small guanine triphosphatases, such as Rac1 and Cdc42. Regarding the mechanism for this effect, we found that STAP-2 associates with Vav1, the guanine-nucleotide exchanging factor for Rac1, and enhances downstream Vav1/Rac1 signaling. These results reveal a novel STAP-2-mediated mechanism for the regulation of SDF-1 alpha-induced chemotaxis of T cells via activation of Vav1/Rac1 signaling. The Journal of Immunology, 2009, 183: 7966-7974.
引用
收藏
页码:7966 / 7974
页数:9
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