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

作者：Cao, Xuan; Kaneko, Tomonori; Li, Jenny S.; Liu, An-Dong; Voss, Courtney; Li, Shawn S. C.^*

来源：Nature Communications, 2015, 6(1): 7721.

DOI：10.1038/ncomms8721

• TUMOR-SUPPRESSOR PTEN
• BREAST-CANCER CELLS
• MEMBRANE ASSOCIATION
• PHOSPHATASE-ACTIVITY
• PROTEIN DLC-1
• C2 DOMAINS
• SH2 DOMAIN
• RAC
• GROWTH
• EGF

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.

• 出版日期2015-7
• 单位华中科技大学