| Title: | Coactivation of G protein signaling by cell-surface receptors and an intracellular exchange factor |
| Address: | "Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, USA" |
| DOI: | 10.1016/j.cub.2008.01.007 |
| ISSN/ISBN: | 0960-9822 (Print) 1879-0445 (Electronic) 0960-9822 (Linking) |
| Abstract: | "G protein-coupled receptors (GPCRs) mediate responses to a broad range of chemical and environmental signals. In yeast, a pheromone-binding GPCR triggers events leading to the fusion of haploid cells. In general, GPCRs function as guanine-nucleotide exchange factors (GEFs); upon agonist binding, the receptor induces a conformational change in the G protein alpha subunit, resulting in exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and in signal initiation. Signaling is terminated when GTP is hydrolyzed to GDP [1]. This well-established paradigm has in recent years been revised to include new components that rates of GDP release, GTP binding [2-8], and GTP hydrolysis[9, 10]. Here we report the discovery of a nonreceptor GEF, Arr4. Like receptors, Arr4 binds directly to the G protein,accelerates guanine-nucleotide exchange, and stabilizes the nucleotide-free state of the a subunit. Moreover, Arr4 promotes G protein-dependent cellular responses, including mitogen-activated protein kinase (MAPK) phosphorylation,new-gene transcription, and mating. In contrast to knownGPCRs, however, Arr4 is not a transmembrane receptor,but rather a soluble intracellular protein. Our data suggest that intracellular proteins function in cooperation with mating pheromones to amplify G protein signaling, thereby leading to full pathway activation" |
| Keywords: | "Adenosine Triphosphatases GTP-Binding Proteins/*metabolism Gene Expression Regulation, Fungal/physiology Guanine Nucleotide Exchange Factors/*genetics/*metabolism Pheromones/metabolism Receptors, Cell Surface/*metabolism Saccharomyces cerevisiae/*metaboli;" |
| Notes: | "MedlineLee, Michael J Dohlman, Henrik G eng P01 GM065533/GM/NIGMS NIH HHS/ R01 GM080739/GM/NIGMS NIH HHS/ F31 MH081472/MH/NIMH NIH HHS/ F31-MH081472/MH/NIMH NIH HHS/ GM065533/GM/NIGMS NIH HHS/ R01 GM073180/GM/NIGMS NIH HHS/ R01 GM080739-03/GM/NIGMS NIH HHS/ R01 GM080739-01/GM/NIGMS NIH HHS/ R01 GM080739-02/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2008/02/12 Curr Biol. 2008 Feb 12; 18(3):211-5. doi: 10.1016/j.cub.2008.01.007" |
