Tyrosine phosphorylation of Rab7 by Src kinase
Tyrosine phosphorylation of Rab7 by Src kinase
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Src 激酶对 Rab7 的酪氨酸磷酸化
DOI：
10.1016/j.cellsig.2017.03.006
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发表时间：
2017-07-01
影响因子：
4.8
通讯作者：
Wang, Tuanlao
中科院分区：
文献类型：
--
作者：
Lin, Xiaosi;Zhang, Jiaming;Wang, Tuanlao
Rab 7是一种小分子量的GTdR，是晚期内体/溶酶体膜转运的关键调节因子，已知Rab 7是磷酸化的，但Rab 7磷酸化的相应激酶及其功能调控尚不清楚。我们提供的证据表明Rab 7是Src激酶的底物，并且被Src酪氨酸磷酸化，Rab 7的Y183残基是Src的最佳磷酸化位点。进一步的研究表明Rab 7的酪氨酸磷酸化依赖于Rab 7的鸟嘌呤核苷酸结合活性和Src激酶的活性。Rab 7的酪氨酸磷酸化是由EGF生理诱导的，并且损害Rab 7与RILP的相互作用，从而抑制EGFR降解并维持Akt信号传导。这些结果表明Rab 7的酪氨酸磷酸化可能参与协调膜运输和细胞信号传导。(C)2017由Elsevier Inc.出版
The small molecular weight GTPase Rab7 is a key regulator for late endosomal/lysosomal membrane trafficking, it was known that Rab7 is phosphorylated, but the corresponding kinase and the functional regulation of Rab7 phosphorylation remain unclear. We provide evidence here that Rab7 is a substrate of Src kinase, and is tyrosine-phosphorylated by Src, withY183 residue of Rab7 being the optimal phosphorylation site for Src. Further investigations demonstrated that the tyrosine phosphorylation of Rab7 depends on the guanine nucleotide binding activity of Rab7 and the activity of Src kinase. The tyrosine phosphorylation of Rab7 is physiologically induced by EGF, and impairs the interaction of Rab7 with RILP, consequently inhibiting EGFR degradation and sustaining Akt signaling. These results suggest that the tyrosine phosphorylation of Rab7 may be involved in coordinating membrane trafficking and cell signaling. (C) 2017 Published by Elsevier Inc.