G Proteins

Mediating Migratory Signals

Science's STKE  13 Jun 2006:
Vol. 2006, Issue 339, pp. tw197
DOI: 10.1126/stke.3392006tw197

G protein-coupled receptors (GPCRs), which make up the largest known protein family, are cell surface receptors that activate heterotrimeric guanine nucleotide-binding proteins (G proteins), which, in turn, activate various downstream signaling pathways and cellular responses. The ubiquitously expressed Gα13 G protein stimulates cell migration in response to activation of the GPCRs that recognize thrombin and lysophosphatidic acid (LPA). Intriguingly, Shan et al. found that cultured mouse embryo fibroblasts (MEFs) lacking Gα13 failed to migrate in response to stimulation with platelet-derived growth factor (PDGF) or epidermal growth factor (EGF), substances that signal through cell surface receptor tyrosine kinases (RTKs) rather than GPCRs. A mutant form of Gα13 that was unable to couple to GPCRs could substitute for wild-type Gα13 in mediating cell migration in response to PDGF or EGF but not in response to LPA. PDGF activated Rac, which acts downstream of the PDGF receptor to mediate cell migration, but constitutively activated Rac failed to stimulate migration in the absence of Gα13. Both in vitro binding assays and coimmunoprecipitation analysis indicated that Rac1 bound to Gα13. Moreover, in MEFs lacking Gα13, PDGF failed to stimulate the translocation of Rac, cortactin, and F-actin polymers to membrane ruffles and lamellipodia at the cell periphery; instead, they localized to dorsal ruffles (ring-shaped structures on the dorsal cell surface). Thus, the authors conclude that Gα13 transmits signals involved in cell migration not only for GPCR-mediated pathways but also for RTK-mediated pathways.

D. Shan, L. Chen, D. Wang, Y.-C. Tan, J. L. Gu, X.-Y. Huang, The G protein Gα13 is required for growth factor-induced cell migration. Dev. Cell. 10, 707-718 (2006). [PubMed]