| Title: | A truncated form of RGS3 negatively regulates G protein-coupled receptor stimulation of adenylyl cyclase and phosphoinositide phospholipase C |
| Author(s): | Chatterjee TK; Eapen AK; Fisher RA; |
| Address: | "Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA" |
| ISSN/ISBN: | 0021-9258 (Print) 0021-9258 (Linking) |
| Abstract: | "Identification of a new family of proteins (RGS proteins) that function as negative regulators of G protein signaling has sparked new understanding of desensitization of this signaling process. Recent studies with several mammalian RGS proteins has delineated their ability to interact with and function as GTPase-activating proteins specifically for G proteins in the Gi family. Here, we investigated the functional activity of RGS3 and a truncated form of RGS3 on G protein-coupled receptor-mediated activation of adenylyl cyclase, phosphoinositide phospholipase C, and mitogen-activated protein kinase in intact cells. Polymerase chain reaction and 5'-rapid amplification of cDNA ends analyses revealed the tissue-specific expression of a short form of the RGS3 transcript that encodes the approximate carboxyl-terminal half of RGS3. This truncated form of RGS3 (RGS3T) was shown recently to function as a negative regulator of pheromone signaling in yeast (Druey, K. M., Blumer, K. J., Kang, V. R., and Kehrl, J. H. (1996) Nature 379, 742-746). Baby hamster kidney cells transiently transfected with RGS3T cDNA exhibited a pronounced impairment in platelet-activating factor receptor-stimulated inositol phosphate production, a pertussis toxin-insensitive response. Similarly, calcitonin gene-related peptide receptor-stimulated increases in intracellular cAMP and pituitary adenylate-cyclase activating polypeptide receptor-stimulated increases in both cAMP and inositol phosphates were reduced significantly in RGS3T transfectants compared with vector-transfected control cells. In contrast, baby hamster kidney cells transfected with the full-length RGS3 cDNA showed no impairment in cAMP and inositol phosphate production mediated by these G protein-coupled receptors. However, lysophosphatidic acid receptor-stimulated phosphorylation of endogenous ERK1 and ERK2 was impaired markedly in both RGS3 and RGS3T transfectants, demonstrating the functional ability of both RGS forms to modulate Gi-mediated signaling. These results provide the first evidence for regulatory effects of an RGS protein on Gs- and Gq-mediated signaling in intact cells and document that the carboxyl-terminal region of RGS3 comprises the structural domain for this activity" |
| Keywords: | "Adenylyl Cyclases/*metabolism Animals Cricetinae Enzyme Activation GTP-Binding Proteins/*metabolism *GTPase-Activating Proteins Phosphatidylinositol Diacylglycerol-Lyase Proteins/chemistry/*metabolism *RGS Proteins Receptors, Cell Surface/*metabolism *Rec;" |
| Notes: | "MedlineChatterjee, T K Eapen, A K Fisher, R A eng DK25295/DK/NIDDK NIH HHS/ HL41071/HL/NHLBI NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 1997/06/13 J Biol Chem. 1997 Jun 13; 272(24):15481-7. doi: 10.1074/jbc.272.24.15481" |
