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
来源：
JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 12期
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.
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收藏
页码：7966 / 7974
页数：9
相关论文
共 40 条
[1]   Chemokines in lymphopoiesis and lymphoid organ development [J].
Ansel, KM ;
Cyster, JG .
CURRENT OPINION IN IMMUNOLOGY, 2001, 13 (02) :172-179
[2]   CrkL plays a role in SDF-1-induced activation of the Raf-1/MEK/Erk pathway through Ras and Rac to mediate chemotactic signaling in hematopoietic cells [J].
Arai, Ayako ;
Aoki, Mae ;
Yan Weihua ;
Jin, Aishun ;
Miura, Osamu .
CELLULAR SIGNALLING, 2006, 18 (12) :2162-2171
[3]   The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry [J].
Bleul, CC ;
Farzan, M ;
Choe, H ;
Parolin, C ;
ClarkLewis, I ;
Sodroski, J ;
Springer, TA .
NATURE, 1996, 382 (6594) :829-833
[4]   A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1) [J].
Bleul, CC ;
Fuhlbrigge, RC ;
Casasnovas, JM ;
Aiuti, A ;
Springer, TA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (03) :1101-1109
[5]   Regulatory and signaling properties of the Vav family [J].
Bustelo, XR .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (05) :1461-1477
[6]   6-C-kine (SLC), a lymphocyte adhesion-triggering chemokine expressed by high endothelium, is an agonist for the MIP-3β receptor CCR7 [J].
Campbell, JJ ;
Bowman, EP ;
Murphy, K ;
Youngman, KR ;
Siani, MA ;
Thompson, DA ;
Wu, LJ ;
Zlotnik, A ;
Butcher, EC .
JOURNAL OF CELL BIOLOGY, 1998, 141 (04) :1053-1059
[7]   Chemokines in tissue-specific and microenvironment-specific lymphocyte homing [J].
Campbell, JJ ;
Butcher, EC .
CURRENT OPINION IN IMMUNOLOGY, 2000, 12 (03) :336-341
[8]   Phylogenetic conservation of the regulatory and functional properties of the Vav oncoprotein family [J].
Couceiro, JR ;
Martín-Bermudo, MD ;
Bustelo, XR .
EXPERIMENTAL CELL RESEARCH, 2005, 308 (02) :364-380
[9]  
del Pozo MA, 1999, EUR J IMMUNOL, V29, P3609
[10]   WIP and WASP play complementary roles in T cell homing and chemotaxis to SDF-1α [J].
Gallego, MD ;
de la Fuente, MA ;
Anton, IM ;
Snapper, S ;
Fuhlbrigge, R ;
Geha, RS .
INTERNATIONAL IMMUNOLOGY, 2006, 18 (02) :221-232
1234