A phosphorylation switch controls the spatiotemporal activation of Rho GTPases in directional cell migration.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26166433.
- Also identified by DOI 10.1038/ncomms8721 and PMC identifier 4510974.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Cell Movement
- GTPase-Activating Proteins
- Microfilament Proteins
- PTEN Phosphohydrolase
- Phosphatidylinositol 3-Kinase
- Tumor Suppressor Proteins
- rac1 GTP-Binding Protein
- rhoA GTP-Binding Protein