Essential role of the T cell-specific adapter protein in the activation of LCK in peripheral T cells.
Essential role of the T cell-specific adapter protein in the activation of LCK in peripheral T cells.
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DOI：
10.1084/jem.20051637
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发表时间：
2006-02-20
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T细胞特异性衔接蛋白（TSAd）是一种含有SRC-同源性-2（SH 2）结构域的细胞内信号传导分子，是T细胞抗原受体（TCR）诱导的T细胞中细胞因子合成所必需的。TSAd如何在TCR信号转导中发挥作用尚不清楚。以前的工作表明，这个适配器的核作用。然而，其他证据表明TSAd也在细胞质中发挥作用。使用TSAd缺陷小鼠的T细胞，我们现在表明，TSAd在细胞质中的主要作用是在TCR信号转导开始时激活LCK蛋白酪氨酸激酶。因此，TSAd调节几个下游信号传导事件，包括细胞内钙动员和Ras-细胞外信号调节激酶信号传导途径的激活。TSAd通过与LCK SH 3和SH 2结构域的物理相互作用直接调节LCK活性。这些研究揭示了TSAd作为近端TCR信号转导的正调节因子，并为TCR诱导的LCK激活机制提供了重要的新信息。
T cell–specific adapter protein (TSAd) is a SRC-homology-2 (SH2) domain–containing intracellular signaling molecule that is required for T cell antigen receptor (TCR)–induced cytokine synthesis in T cells. How TSAd functions in TCR signal transduction is not clear. Previous work has suggested a nuclear role for this adapter. However, other evidence suggests that TSAd also functions in the cytoplasm. Using T cells from TSAd-deficient mice, we now show that the major role of TSAd in the cytoplasm is in activation of the LCK protein tyrosine kinase at the outset of TCR signal transduction. Consequently, TSAd regulates several downstream signaling events, including intracellular calcium mobilization and activation of the Ras–extracellular signal–regulated kinase signaling pathway. TSAd regulates LCK activity directly through physical interaction with LCK SH3 and SH2 domains. These studies reveal TSAd as a positive regulator of proximal TCR signal transduction and provide important new information on the mechanism of TCR-induced LCK activation.