T cell receptor activation leads to two distinct phases of Pyk2 activation and actin cytoskeletal rearrangement in human T cells
T cell receptor activation leads to two distinct phases of Pyk2 activation and actin cytoskeletal rearrangement in human T cells
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DOI：
10.1016/j.molimm.2010.03.009
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发表时间：
2010-05-01
影响因子：
3.6
通讯作者：
Houtman, Jon C. D.
中科院分区：
文献类型：
--
作者：
Collins, Michaela;Bartelt, Rebekah R.;Houtman, Jon C. D.
酪氨酸激酶Pyk2整合了受体介导的信号，控制肌动蛋白细胞骨架重排，这是T细胞激活和功能所需的事件。T细胞受体（TCR）的诱导导致Pyk2的磷酸化，但这些事件的时间是有争议的，并没有完全理解。本研究表征了tcr诱导的Pyk2酪氨酸402和580在人T细胞中的磷酸化动力学。有趣的是，早期tcr介导的Pyk2磷酸化比ZAP-70更快速和短暂，其磷酸化动力学与其他T细胞信号蛋白相似。出乎意料的是，在TCR刺激后30-60分钟，Pyk2发生了第二次磷酸化爆发。Pyk2在两次单独的磷酸化爆发中具有酶活性，因为paxillin磷酸化（Pyk2的已知底物）和tcr诱导的肌动蛋白聚合表现出相似的动力学。Pyk2磷酸化的第二次爆发不需要肌动蛋白细胞骨架重排或PI3K功能，而是依赖于Fyn和/或Lck的酶活性。总的来说，这些观察结果表明，TCR激活的下游信号通路是硬连线的，可诱导Pyk2激活和肌动蛋白细胞骨架重排两个独立的时期。(C) 2010 Elsevier Ltd.版权所有。
The tyrosine kinase Pyk2 integrates receptor-mediated signals controlling actin cytoskeletal rearrangement, events needed for the activation and function of T cells. Induction of the T cell receptor (TCR) leads to the phosphorylation of Pyk2, but the timing of these events is controversial and not fully understood. In this study, the TCR-induced phosphorylation kinetics of Pyk2 tyrosines 402 and 580 were characterized in human T cells. Interestingly, the early TCR-mediated phosphorylation of Pyk2 was more rapid and transient than ZAP-70, whose phosphorylation kinetics were similar to other T cell signaling proteins. Unexpectedly, Pyk2 had a second burst of phosphorylation 30-60 min after TCR stimulation. Pyk2 was enzymatically active during the two separate bursts of phosphorylation, since both paxillin phosphorylation, a known substrate of Pyk2, and TCR-induced actin polymerization showed similar kinetics. The second burst of Pyk2 phosphorylation did not require actin cytoskeleton rearrangement or PI3K function, but was dependent on the enzymatic activity of Fyn and/or Lck. Collectively, these observations suggest that signaling pathways downstream of TCR activation are hard-wired to induce two separate periods of Pyk2 activation and actin cytoskeletal rearrangement. (C) 2010 Elsevier Ltd. All rights reserved.