Requirement for the SLP-76 adaptor CADS in T cell development

被引:124
作者
Yoder, J
Pham, C
Iizuka, YM
Kanagawa, O
Liu, SK
McGlade, J
Cheng, AM [1 ]
机构
[1] Washington Univ, Sch Med, Ctr Immunol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Med Sci Training Program, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA
[4] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[5] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada
关键词
D O I
10.1126/science.1057176
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
GADS is an adaptor protein implicated in CD3 signaling because of its ability to link SLP-76 to LAT. A GADS-deficient mouse was generated by gene targeting, and the function of GADS in T cell development and activation was examined. GADS(-) CD4(-)CD8(-) thymocytes exhibited a severe block in proliferation but still differentiated into mature T cells. GADS(-) thymocytes failed to respond to CD3 cross-linking in vivo and were-impaired in positive and negative selection. Immunoprecipitation experiments revealed that the association between SLP-76 and LAT was uncoupled in GADS(-) thymocytes. These observations indicate that CADS is a critical adaptor for CD3 signaling.
引用
收藏
页码:1987 / 1991
页数:5
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