Yoder J, Pham C, Iizuka Y M, Kanagawa O, Liu S K, McGlade J, Cheng A M
Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, USA.
Science. 2001 Mar 9;291(5510):1987-91. doi: 10.1126/science.1057176.
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 GADS is a critical adaptor for CD3 signaling.
GADS是一种衔接蛋白，因其能够将SLP-76与LAT相连而参与CD3信号传导。通过基因打靶构建了GADS缺陷小鼠，并研究了GADS在T细胞发育和激活中的功能。GADS缺陷的CD4-CD8-胸腺细胞在增殖方面表现出严重阻滞，但仍能分化为成熟T细胞。GADS缺陷的胸腺细胞在体内对CD3交联无反应，且在阳性和阴性选择中受损。免疫沉淀实验表明，在GADS缺陷的胸腺细胞中，SLP-76与LAT之间的关联被解除。这些观察结果表明，GADS是CD3信号传导的关键衔接蛋白。
