Tyrosine phosphorylation of Rab7 by Src kinase.
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.
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.
Xiaosi
X
Lin
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.
Jiaming
J
Zhang
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.
Lingqiu
L
Chen
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.
Yongjun
Y
Chen
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.
Xiaohui
X
Xu
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.
Wanjin
W
Hong
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. Electronic address: xmuibrwtl@xmu.edu.cn.
Tuanlao
T
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport / Q000235:genetics*; D059748:Proteolysis; D015398:Signal Transduction / Q000235:genetics*; D014443:Tyrosine / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics*; D000090802:rab7 GTP-Binding Proteins; D019061:src-Family Kinases / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; C423317:RILP protein, human; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D014443:Tyrosine; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D019061:src-Family Kinases; D020691:rab GTP-Binding Proteins
RILP; Rab phosphorylation; Rab7; Src