The effects of membrane compartmentalization of csk on TCR signaling.
The effects of membrane compartmentalization of csk on TCR signaling.
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csk 膜区室化对 TCR 信号传导的影响。
DOI：
10.1016/j.bbamcr.2010.12.003
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
T. Brdicka
中科院分区：
文献类型：
--
作者：
P. Otáhal;S. Pata;P. Angelisová;V. Hořejší;T. Brdicka
TCR信号转导由Src家族激酶（SFK）的激活启动，所述Src家族激酶（SFK）磷酸化存在于T细胞受体（TCR）信号传导亚基的细胞内部分中的基于免疫受体酪氨酸的激活基序（ITAM）。大量数据表明，刺激后TCR与膜筏相互作用，从而获得SFK和其他参与信号转导的重要分子。然而，这一过程的确切机制尚不清楚。关键问题之一是SFK如何进入TCR以及非筏和膜筏相关的SFK对于TCR信号传导的启动和维持的重要性。为了回答这个问题，我们将SFK的负调节因子C-末端Src激酶（Csk）靶向膜筏，最近描述为“重筏”或非筏膜。我们的数据表明，只有Csk靶向“经典”筏，而不是“重筏”或非筏膜有效地抑制TCR信号转导，证明膜筏相关的SFK在这个过程中的关键作用。
The TCR signal transduction is initiated by the activation of Src-family kinases (SFK) which phosphorylate Immunoreceptor tyrosine-based activation motifs (ITAM) present in the intracellular parts of the T-cell receptor (TCR) signaling subunits. Numerous data suggest that after stimulation TCR interacts with membrane rafts and thus it gains access to SFK and other important molecules involved in signal transduction. However, the precise mechanism of this process is unclear. One of the key questions is how SFK access TCR and what is the importance of non-raft and membrane raft-associated SFK for the initiation and maintenance of the TCR signaling. To answer this question we targeted a negative regulator of SFK, C-terminal Src kinase (Csk) to membrane rafts, recently described “heavy rafts” or non-raft membrane. Our data show that only Csk targeted into “classical” raft but not to “heavy raft” or non-raft membrane effectively inhibits TCR signaling, demonstrating the critical role of membrane raft-associated SFK in this process.