Uncoupling of nonreceptor tyrosine kinases from PLC-γ1 in an SLP-76-deficient T cell
Uncoupling of nonreceptor tyrosine kinases from PLC-γ1 in an SLP-76-deficient T cell
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DOI：
10.1126/science.281.5375.413
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发表时间：
1998-07-17
期刊：
影响因子：
56.9
通讯作者：
Weiss, A
中科院分区：
文献类型：
--
作者：
Yablonski, D;Kuhne, MR;Weiss, A
非受体蛋白酪氨酸激酶（PTK）的激活对于T细胞受体（TCR）反应性是必不可少的;然而，单个PTK底物的功能通常是不确定的。分离了突变T细胞系，其缺乏SLP-76（76千道尔顿的含SH 2结构域的白细胞蛋白）、造血表达的衔接蛋白和PTK底物的表达。SLP-76对于TCR诱导的大多数蛋白质的酪氨酸磷酸化不是必需的，但是对于磷脂酶C-γ 1（PLC-γ 1）的最佳酪氨酸磷酸化和活化以及Ras途径活化是必需的。TCR诱导的基因表达依赖于SLP-76。因此，TCR调节的PTK与下游信号传导途径的偶联需要SLP-76。
Activation of nonreceptor protein tyrosine kinases (PTKs) is essential for T cell receptor (TCR) responsiveness; however, the function of individual PTK substrates is often uncertain. A mutant T cell Line was isolated that Lacked expression of SLP-76 (SH2 domain-containing Leukocyte protein of 76 kilodaltons), a hematopoietically expressed adaptor protein and PTK substrate. SLP-76 was not required for TCR-induced tyrosine phosphorylation of most proteins, but was required for optimal tyrosine phosphorylation and activation of phospholipase C-gamma l (PLC-gamma l), as well as Ras pathway activation. TCR-inducible gene expression was dependent on SLP-76. Thus, coupling of TCR-regulated PTKs to downstream signaling pathways requires SLP-76.