Tyrosine phosphorylation of p62Dok induced by cell adhesion and insulin:: possible role in cell migration
Tyrosine phosphorylation of p62Dok induced by cell adhesion and insulin:: possible role in cell migration
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DOI：
10.1093/emboj/18.7.1748
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发表时间：
1999-04-01
期刊：
影响因子：
11.4
通讯作者：
Kasuga, M
中科院分区：
文献类型：
--
作者：
Noguchi, T;Matozaki, T;Kasuga, M
Dok, a 62-kDa Ras GTPase-activating protein (ras-GAP)-associated phosphotyrosyl protein, is thought to act as a multiple docking protein downstream of receptor or non-receptor tyrosine kinases, Cell adhesion to extracellular matrix proteins induced marked tyrosine phosphorylation of Dok, This adhesion-dependent phosphorylation of Dok was mediated, at least in part, by Src family tyrosine kinases, The maximal insulin-induced tyrosine phosphorylation of Dok required a Src family kinase, A mutant Dok (Dok Delta PH) that lacked its pleckstrin homology domain failed to undergo tyrosine phosphorylation in response to cell adhesion or insulin. Furthermore, unlike the wild-type protein, Dok Delta PH did not localize to subcellular membrane components. Insulin promoted the association of tyrosine-phosphorylated Dok with the adapter protein NCK and rasGAP, In contrast, a mutant Dok (DokY361F), in which Tyr361 was replaced by phenylalanine, failed to bind NCK but partially retained the ability to bind rasGAP in response to insulin. Overexpression of wild-type Dok, but not that of Dok Delta PH or DokY361F, enhanced the cell migratory response to insulin without affecting insulin activation of mitogen-activated protein kinase, These results identify Dok as a signal transducer that potentially links, through its interaction with NCK or rasGAP, cell adhesion and insulin receptors to the machinery that controls cell motility.
