The membrane-proximal portion of CD3 ∈ associates with the serine/threonine kinase GRK2
The membrane-proximal portion of CD3 ∈ associates with the serine/threonine kinase GRK2
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DOI：
10.1074/jbc.m609418200
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发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
van Oers, Nicolai S. C.
中科院分区：
文献类型：
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作者：
DeFord-Watts, Laura M.;Young, Jennifer A.;van Oers, Nicolai S. C.
蛋白激酶的激活是T细胞受体（TCR）传播细胞内信号的主要机制之一。迄今为止，已知参与TCR信号传导早期阶段的大多数激酶是蛋白酪氨酸激酶，例如Lck、Fyn和ZAP-70。在这里，我们报告的组成性协会之间的TCR和丝氨酸/苏氨酸激酶，这是通过介导的膜近端部分的CD 3 γ。CD 3 ε相关蛋白质的质谱分析鉴定G蛋白偶联受体激酶2（GRK 2）为候选Ser/Thr激酶。瞬时转染试验和Western印迹分析证实了GRK 2与细胞内CD 3+胞质结构域相互作用的能力。这些发现与最近的报道一致，这些报道证明某些G蛋白偶联受体（GPCR）和G蛋白能够与α/β TCR物理结合。由于GRK 2主要参与阻止GPCR信号，因此其与CD 3 γ的相互作用可能提供一种新的手段，由此TCR可以负调节通过GPCR产生的信号。
The activation of protein kinases is one of the primary mechanisms whereby T cell receptors (TCR) propagate intracellular signals. To date, the majority of kinases known to be involved in the early stages of TCR signaling are protein-tyrosine kinases such as Lck, Fyn, and ZAP-70. Here we report a constitutive association between the TCR and a serine/threonine kinase, which was mediated through the membrane-proximal portion of CD3 epsilon. Mass spectrometry analysis of CD3 epsilon-associated proteins identified G protein-coupled receptor kinase 2 (GRK2) as a candidate Ser/Thr kinase. Transient transfection assays and Western blot analysis verified the ability of GRK2 to interact with the cytoplasmic domain of CD3 epsilon within a cell. These findings are consistent with recent reports demonstrating the ability of certain G protein-coupled receptors (GPCR) and G proteins to physically associate with the alpha/beta TCR. Because GRK2 is primarily involved in arresting GPCR signals, its interaction with CD3 epsilon may provide a novel means whereby the TCR can negatively regulate signals generated through GPCRs.