A phosphorylation switch controls the spatiotemporal activation of Rho GTPases in directional cell migration

被引:36
|
作者
Cao, Xuan [1 ,2 ]
Kaneko, Tomonori [1 ]
Li, Jenny S. [3 ]
Liu, An-Dong [2 ]
Voss, Courtney [1 ]
Li, Shawn S. C. [1 ,4 ]
机构
[1] Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada
[2] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Med Genet, Tongji Med Coll, Wuhan 430030, Peoples R China
[3] Univ Western Ontario, Schulich Sch Med & Dent, Dept Med, London, ON N6A 5C1, Canada
[4] Childrens Hlth Res Inst, London, ON N6C 2V5, Canada
来源
NATURE COMMUNICATIONS | 2015年 / 6卷
关键词
TUMOR-SUPPRESSOR PTEN; BREAST-CANCER CELLS; MEMBRANE ASSOCIATION; PHOSPHATASE-ACTIVITY; PROTEIN DLC-1; C2; DOMAINS; SH2; DOMAIN; RAC; GROWTH; EGF;
D O I
10.1038/ncomms8721
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Although cell migration plays a central role in development and disease, the underlying molecular mechanism is not fully understood. Here we report that a phosphorylation-mediated molecular switch comprising deleted in liver cancer 1 (DLC1), tensin-3 (TNS3), phosphatase and tensin homologue (PTEN) and phosphoinositide-3-kinase (PI3K) controls the spatiotemporal activation of the small GTPases, Rac1 and RhoA, thereby initiating directional cell migration induced by growth factors. On epidermal growth factor (EGF) or platelet-derived growth factor (PDGF) stimulation, TNS3 and PTEN are phosphorylated at specific Thr residues, which trigger the rearrangement of the TNS3-DLC1 and PTEN-PI3K complexes into the TNS3-PI3K and PTEN-DLC1 complexes. Subsequently, the TNS3-PI3K complex translocates to the leading edge of a migrating cell to promote Rac1 activation, whereas PTEN-DLC1 translocates to the posterior for localized RhoA activation. Our work identifies a core signalling mechanism by which an external motility stimulus is coupled to the spatiotemporal activation of Rac1 and RhoA to drive directional cell migration.
引用
收藏
页数:14
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