Transducing the signals: a G protein takes a new identity.
The prevailing dogma is that heterotrimeric G proteins exclusively transduce signals from the seven-transmembrane motif-containing cell surface receptors, also known as G protein-coupled receptors (GPCRs). New evidence indicates that Galpha(13), the alpha subunit of the G protein G(13), breaks away from this traditional exclusive signaling alliance with GPCRs to transmit signals from receptor tyrosine kinases (RTKs), such as platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptor (VEGFR). Galpha(13) is involved in cell migration in response to GPCRs activated by lysophosphatidic acid (LPA) or thrombin. A new report indicates that Galpha(13) is also required for cell migration induced by the growth factors, such as PDGF, EGF, or VEGF. GPCR coupling is not required for such RTK-to-Galpha(13) signaling. This new identity for Galpha(13) as a signal transducer for both GPCRs and RTKs may be a forerunner for similar findings involving other Galpha subunits. This expanding role of G proteins in both GPCR signaling and RTK signaling is likely to have a great impact not only on our understanding of cell signaling in general, but also more specifically where the dysregulation of signaling by GPCRs, RTKs, and G proteins cause pathophysiological changes such as in the case of tumorigenesis, tumor progression and/or metastasis.
Dhanasekaran
Danny N
DN
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA. danny001@temple.edu
D000818:Animals; D002465:Cell Movement; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000502:physiology*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction
D043562:Receptors, G-Protein-Coupled; D020794:Receptor Protein-Tyrosine Kinases; D044365:GTP-Binding Protein alpha Subunits, G12-G13