Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity
Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity
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DOI：
10.1126/science.284.5414.638
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发表时间：
1999-04-23
期刊：
影响因子：
56.9
通讯作者：
Schwartzberg, PL
中科院分区：
文献类型：
--
作者：
Schaeffer, EM;Debnath, J;Schwartzberg, PL
T细胞受体（TCR）信号传导需要激活Zap-70和Src家族酪氨酸激酶，但对其他酪氨酸激酶的要求不太清楚。合并删除;两种Tec激酶Rlk和Itk的小鼠在体外引起TCR应答的显著缺陷，包括增殖、细胞因子产生和凋亡，以及在体内引起对弓形虫的适应性免疫应答。在rlk（-/-）itk（-/-）细胞中，紧邻TCR下游的分子事件是完整的，但中间事件包括三磷酸肌醇产生、钙动员和促分裂原活化蛋白激酶活化被削弱，从而确立Tec激酶作为磷脂酶C-γ活化所需的TCR信号传导的关键调节剂。
T cell receptor (TCR) signaling requires activation of Zap-70 and Src family tyrosine kinases, but requirements for other tyrosine kinases are Less clear. Combined deletion in;mice of two Tec kinases, Rlk and Itk, caused marked defects in TCR responses including proliferation, cytokine production, and apoptosis in vitro and adaptive:immune responses to Toxoplasma gondii in vivo. Molecular events immediately downstream from the TCR were intact in rlk(-/-)itk(-/-) cells, but intermediate events including inositol trisphosphate production, calcium mobilization, and mitogen-activated protein kinase activation were impaired, establishing Tec kinases as critical regulators of TCR signaling required for phospholipase C-gamma activation.