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首页> 外文期刊>Molecular and Cellular Biology >The nonreceptor protein-tyrosine kinase CSK complexes directly with the GTPase-activating protein-associated p62 protein in cells expressing v-Src or activated c-Src.
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The nonreceptor protein-tyrosine kinase CSK complexes directly with the GTPase-activating protein-associated p62 protein in cells expressing v-Src or activated c-Src.

机译：非受体蛋白-酪氨酸激酶CSK直接与表达v-Src或激活的c-Src的细胞中的GTPase激活蛋白相关的p62蛋白复合。

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CSK is a predominantly cytosolic protein-tyrosine kinase (PTK) that negatively regulates Src family PTKs by phosphorylation of a conserved tyrosine near their C termini. Little is known about how CSK itself is regulated. On the basis of immunofluorescence studies, a model has been proposed that when c-Src is activated, it is redistributed to podosomes, in which substrates become phosphorylated, creating binding sites for CSK. CSK is recruited to these sites of c-Src activation via its SH2 and SH3 domains and is then in a position to downregulate c-Src activity (B. W. Howell and J. A. Cooper, Mol. Cell. Biol. 14:5402-5411, 1994). To identify phosphotyrosine (P.Tyr)-containing proteins that may mediate translocation of CSK due to c-Src activation, we have examined the whole spectrum of P.Tyr-containing proteins that associate with CSK in v-Src NIH 3T3 cells by anti-P.Tyr immunoblotting. Nine P.Tyr-containing proteins coimmunoprecipitated with CSK from v-Src NIH 3T3 cells. One of these, an approximately 62-kDa protein, also associated with CSK in NIH 3T3 cells treated with vanadate prior to lysis and in NIH 3T3 cells expressing an activated c-Src mutant. This 62-kDa protein was shown to be identical to the GTPase-activating protein (GAP)-associated p62 (GAP-A.p62) protein. The interaction between CSK and GAP-A.p62 could be reconstituted in vitro with glutathione S-transferase fusion proteins containing full-length CSK or the CSK SH2 domain. Furthermore, our data show that CSK interacts directly with GAP.A-p62 and that the complex between the two proteins is localized in subcellular membrane or cytoskeletal fractions. Our results suggest that GAP-A.p62 may function as a docking protein and may mediate translocation of proteins, including GAP and CSK, to membrane or cytoskeletal regions upon c-Src activation.
机译：CSK是主要的胞质蛋白酪氨酸激酶（PTK），通过C末端附近的保守酪氨酸磷酸化来负调控Src家族PTK。关于CSK本身如何监管知之甚少。在免疫荧光研究的基础上，有人提出了一个模型，当c-Src被激活时，它会重新分布到足小体上，其中的底物被磷酸化，形成CSK的结合位点。 CSK通过其SH2和SH3结构域募集到c-Src激活的这些位点，然后下调c-Src活性（BW Howell和JA Cooper，Mol。Cell。Biol。14：5402-5411，1994）。 。为了鉴定可能介导c-Src活化引起的CSK易位的含磷酸酪氨酸（P.Tyr）的蛋白，我们研究了通过v-Src NIH 3T3细胞与CSK相关的含P.Tyr的蛋白的全谱-P.Tyr免疫印迹。九种含P.Tyr的蛋白质与CSK从v-Src NIH 3T3细胞共免疫沉淀。其中之一，大约62kDa的蛋白质，在裂解前用钒酸盐处理的NIH 3T3细胞中和表达活化c-Src突变体的NIH 3T3细胞中也与CSK有关。该62 kDa蛋白显示与GTPase激活蛋白（GAP）相关的p62（GAP-A.p62）蛋白相同。 CSK和GAP-A.p62之间的相互作用可以用含有全长CSK或CSK SH2结构域的谷胱甘肽S-转移酶融合蛋白在体外重建。此外，我们的数据表明CSK与GAP.A-p62直接相互作用，并且两种蛋白之间的复合物位于亚细胞膜或细胞骨架部分。我们的结果表明，GAP-A.p62可能充当对接蛋白，并可能在c-Src激活后介导包括GAP和CSK在内的蛋白质向膜或细胞骨架区域的转运。

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