AN RNA-BINDING PROTEIN ASSOCIATED WITH SRC THROUGH ITS SH2 AND SH3 DOMAINS IN MITOSIS
AN RNA-BINDING PROTEIN ASSOCIATED WITH SRC THROUGH ITS SH2 AND SH3 DOMAINS IN MITOSIS
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DOI：
10.1038/368867a0
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发表时间：
1994-04-28
期刊：
影响因子：
64.8
通讯作者：
SHALLOWAY, D
中科院分区：
文献类型：
--
作者：
TAYLOR, SJ;SHALLOWAY, D
在有丝分裂过程中，c-Src的酪氨酸激酶活性通过其调节的酪氨酸残基(1-3)的去磷酸化而被刺激。这与其Src同源-2(SH2)结构域更容易与含有磷酸酪氨酸的多肽(4)结合有关。但激活的c-Src在有丝分裂中的生理靶点尚未确定。在此，我们报道了在小鼠成纤维细胞有丝分裂过程中，68K蛋白(P68)被酪氨酸磷酸化，并与Src发生物理联系。P68在体外独立地与Src SH2和SH3结构域结合，在体内这两个结构域都是p68磷酸化和结合所必需的。P68与P62蛋白密切相关，P62蛋白与Ras GTP酶激活蛋白(GAP)(5)相关，并选择性地直接或间接地与多聚核苷酸结合。由于Src SH3结构域还与异质核糖核蛋白K结合，这些结果提出了一种有趣的可能性，即c-Src可能以细胞周期依赖的方式调节RNA的加工、运输或翻译。
THE tyrosine kinase activity of c-Src is stimulated during mitosis by dephosphorylation of its regulatory tyrosine residue(1-3). This is associated with increased accessibility of its Src homology-2 (SH2) domain for binding a phosphotyrosine-containing peptide(4). But physiological targets of activated c-Src in mitosis have not yet been identified. Here we report that a 68K protein (p68) becomes tyrosine-phosphorylated and physically associates with Src during mitosis in mouse fibroblasts. p68 independently binds the Src SH2 and SH3 domains in vitro and both domains are required for p68 phosphorylation and binding in vivo. p68 is closely related to the p62 protein that is associated with the Ras GTPase-activating protein (GAP)(5) and selectively binds, directly or indirectly, polyribonucleotides. Because the Src SH3 domain also binds heterogeneous nuclear ribonucleoprotein K, these results raise the intriguing possibility that c-Src may regulate the processing, trafficking or translation of RNA in a cell-cycle-dependent manner.