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

Xuan Cao, Tomonori Kaneko, Jenny S. Li, An-Dong Liu, Courtney Voss and Shawn S. C. Li ()
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Xuan Cao: Schulich School of Medicine and Dentistry, Western University
Tomonori Kaneko: Schulich School of Medicine and Dentistry, Western University
Jenny S. Li: Schulich School of Medicine and Dentistry, Western University
An-Dong Liu: School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology
Courtney Voss: Schulich School of Medicine and Dentistry, Western University
Shawn S. C. Li: Schulich School of Medicine and Dentistry, Western University

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms8721

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