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

• DOI: 10.1038/ncomms8721
• Publication Date: 2015-07-13T09:43:51Z
• Authors: Xuan Cao; Tomonori Kaneko; Jenny S. Li; An-Dong Liu; Courtney Voss; Shawn S. C. Li
• Keywords: Tensin; RHEB; Small GTPase; Phosphoinositide 3-kinase

Abstract Although cell migration plays a central role in development and disease, the underlying molecular mechanism is not fully understood. Here we report that phosphorylation-mediated switch comprising deleted liver cancer 1 (DLC1), tensin-3 (TNS3), phosphatase tensin homologue (PTEN) phosphoinositide-3-kinase (PI3K) controls spatiotemporal activation of small GTPases, Rac1 RhoA, thereby initiating directional induced by growth factors. On epidermal factor (EGF) or platelet-derived (PDGF) stimulation, TNS3 PTEN are phosphorylated at specific Thr residues, which trigger rearrangement TNS3–DLC1 PTEN–PI3K complexes into TNS3–PI3K PTEN–DLC1 complexes. Subsequently, complex translocates to leading edge migrating promote activation, whereas posterior for localized RhoA activation. Our work identifies core signalling an external motility stimulus coupled drive migration.