Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the Up-regulation of TCR-driven IL-2 transcription requires SLP-76 binding to FYB at Tyr595 and Tyr651.
Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the Up-regulation of TCR-driven IL-2 transcription requires SLP-76 binding to FYB at Tyr595 and Tyr651.
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DOI：
10.4049/jimmunol.163.11.5753
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发表时间：
1999-12
影响因子：
4.4
通讯作者：
L. Geng;M. Raab;C. Rudd
中科院分区：
文献类型：
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作者：
L. Geng;M. Raab;C. Rudd
SLP-76 （Src同源性（SH） 2-结构域含白细胞蛋白76 kDa）和FYB/SLAP （fyn - t结合蛋白/SLP-76相关蛋白）是tcr激活蛋白酪氨酸激酶下游的两个造血细胞特异性衔接蛋白。SLP-76被认为是T细胞信号传导的重要组成部分。FYB被FYN-T选择性磷酸化，为FYN-T和SLP-76 SH2结构域的募集提供了模板。fynt、FYB和SLP-76的共表达可以协同上调TCR连接后T细胞中IL-2的产生。在本报告中，我们发现FYB的两个酪氨酸Tyr595和Tyr651是FYN-T磷酸化的主要位点，并介导Jurkat T细胞与SLP-76的结合。此外，FYN-T-FYB-SLP-76通路中IL-2启动子活性的协同上调取决于FYB和SLP-76的相互作用，而不是FYB和FYN-T的相互作用。这些观察结果确定了SLP-76与下游成分相互作用的途径，从而上调T细胞细胞因子的产生。
SLP-76 (Src homology (SH) 2-domain-containing leukocyte protein of 76 kDa) and FYB/SLAP (FYN-T-binding protein/SLP-76-associated protein) are two hemopoietic cell-specific adaptor proteins downstream of TCR-activated protein tyrosine kinases. SLP-76 has been implicated as an essential component in T cell signaling. FYB is selectively phosphorylated by FYN-T, providing a template for the recruitment of FYN-T and SLP-76 SH2 domains. Coexpression of FYN-T, FYB, and SLP-76 can synergistically up-regulate IL-2 production in T cells upon TCR ligation. In this report, we show that two tyrosines, Tyr595 and Tyr651, of FYB are major sites of phosphorylation by FYN-T and mediate binding to SLP-76 in Jurkat T cells. Furthermore, the synergistic up-regulation of IL-2 promoter activity in the FYN-T-FYB-SLP-76 pathway is contingent upon the interaction between FYB and SLP-76, but not the interaction between FYB and FYN-T. These observations define a pathway by which SLP-76 interacts with downstream components in the up-regulation of T cell cytokine production.