HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse
HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse
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DOI：
10.1016/j.immuni.2006.03.022
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发表时间：
2006-06-01
期刊：
影响因子：
32.4
通讯作者：
Burkhardt, Janis K.
中科院分区：
文献类型：
--
作者：
Gomez, Timothy S.;McCarney, Sean D.;Burkhardt, Janis K.
HS 1是白细胞特异性的皮质激素同源物，在体外调节F-肌动蛋白，并在TCR连接后磷酸化，但其在淋巴细胞活化中的作用尚未得到解决。我们证明，HS 1缺陷的T细胞不能积累F-肌动蛋白在免疫突触（IS），并在TCR连接，形成肌动蛋白丰富的结构是无序和不稳定的。早期TCR活化事件在这些细胞中是完整的，但Ca 2+内流和IL-2基因转录是有缺陷的。重要的是，HS 1酪氨酸磷酸化是其靶向IS和其调节肌动蛋白动力学和IL-2启动子活性的功能所必需的。磷酸化还将HS 1与多种信号蛋白（包括Lck、PLC γ 1和Vav 1）联系起来，并且对于Vav 1稳定募集到IS至关重要。总之，我们的研究表明，HS 1是必不可少的信号事件，导致肌动蛋白组装和IL-2的生产过程中T细胞活化。
HS1, the leukocyte-specific homolog of cortactin, regulates F-actin in vitro and is phosphorylated in response to TCR ligation, but its role in lymphocyte activation has not been addressed. We demonstrate that HS1-deficient T cells fail to accumulate F-actin at the immune synapse (IS) and, upon TCR ligation, form actin-rich structures that are disordered and unstable. Early TCR activation events are intact in these cells, but Ca2+ influx and IL-2 gene transcription are defective. Importantly, HS1 tyrosine phosphorylation is required for its targeting to the IS and for its function in regulating actin dynamics and IL-2 promoter activity. Phosphorylation also links HS1 to multiple signaling proteins, including Lck, PLC gamma 1, and Vav1, and is essential for the stable recruitment of Vav1 to the IS. Taken together, our studies show that HS1 is indispensable for signaling events leading to actin assembly and IL-2 production during T cell activation.