title: G protein coupled growth factor receptor tyrosine kinase: no longer an oxymoron.
abstract: Environmental cues are transmitted to the interior of the cell via a complex network of signaling hubs. Receptor tyrosine kinases (RTKs) and trimeric G proteins are 2 such major signaling hubs in eukaryotes. Canonical signal transduction via trimeric G proteins is spatially and temporally restricted, i.e., triggered exclusively at the plasma membrane (PM) by agonist activation of G-protein-coupled receptors (GPCRs) via a process that completes within a few hundred milliseconds. Recently, a rapidly emerging paradigm has revealed a non-canonical pathway for activation of trimeric G proteins by the non-receptor GEF, GIV/Girdin, that has distinctive temporal and spatial features. Such activation can be triggered by multiple growth factor RTKs, can occur at the PM and on internal membranes discontinuous with the PM, and can continue for prolonged periods of time. The molecular mechanisms that govern such non-canonical G protein activation and the relevance of this new paradigm in health and disease is discussed.
authors.affiliation: a Department of Medicine ; University of California at San Diego ; La Jolla , CA USA.
authors.forename: Pradipta
authors.initials: P
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D060066:Protein Interaction Maps; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D043562:Receptors, G-Protein-Coupled; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020962:Heterotrimeric GTP-Binding Proteins
keywords: G protein -coupled receptors; GIV; girdin; growth factor receptor tyrosine kinases; heterotrimeric G proteins