Lin Xiaosi, Zhang Jiaming, Chen Lingqiu, Chen Yongjun, Xu Xiaohui, Hong Wanjin, Wang Tuanlao
School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian 361005, China.
School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian 361005, China; Institute of Molecular and Cell Biology, A STAR(Agency of Science, Technology and Research), 61 Biopolis Drive, Singapore 138673, Singapore.
Cell Signal. 2017 Jul;35:84-94. doi: 10.1016/j.cellsig.2017.03.006. Epub 2017 Mar 21.
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.
小分子量GTP酶Rab7是晚期内体/溶酶体膜运输的关键调节因子，已知Rab7会发生磷酸化，但其相应的激酶以及Rab7磷酸化的功能调节仍不清楚。我们在此提供证据表明，Rab7是Src激酶的底物，可被Src酪氨酸磷酸化，Rab7的Y183残基是Src的最佳磷酸化位点。进一步研究表明，Rab7的酪氨酸磷酸化取决于Rab7的鸟嘌呤核苷酸结合活性和Src激酶的活性。Rab7的酪氨酸磷酸化在生理上由表皮生长因子（EGF）诱导，会损害Rab7与RILP的相互作用，从而抑制表皮生长因子受体（EGFR）的降解并维持Akt信号传导。这些结果表明，Rab7的酪氨酸磷酸化可能参与协调膜运输和细胞信号传导。
