Mediating Migratory Signals

Abstract

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 Gα 13 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 Gα 13 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 Gα 13 that was unable to couple to GPCRs could substitute for wild-type Gα 13 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 Gα 13 . Both in vitro binding assays and coimmunoprecipitation analysis indicated that Rac1 bound to Gα 13 . Moreover, in MEFs lacking Gα 13 , 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 Gα 13 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 Gα 13 is required for growth factor-induced cell migration. Dev. Cell. 10 , 707-718 (2006). [PubMed]