Recent identification of a family of proteins that function as negative regulators of G protein signaling has provoked new understanding of desensitization of this signaling process. Several RGS proteins have been shown to interact with and function as GTPase-activating proteins specifically for G proteins in the (;, family. Here, we investigated the functional activity of RGS3 and a truncated form of RGS3 (RGS3T) on (; protein-coupled receptormediated activation of MAP kinase, adenylyl cyclase and phosphoinositide phospholipase C ill intact cells. RGS3T transcripts encode the approximate carboxyl terminal half of R(;S3 and are expressed in a tissue-specific manner. BHK cells transiently transfected with RGS3 or RGS3T cDNAs showed a marked reduction in lysophosphatidic acid-stimulated tyrosine phosphorylation of ERK1 and ERK2. BHK cells transfected with RGS3T eDNA but not those transfected with RGS3 eDNA exhibited a pronounced impairment in platelet-activating factor- or pituitary-adenylate cyclase-activating polypeptide (PA(?AP)-stimulated inositol phosphate production and in calcitonin generelated peptide- or PACAP stimulated intracellular cAMP production. These results provide the first evidence for regulatory effects of an RGS protein on Gs- or (;mediated signaling pathways in intact cells and document that the carboxyl terminal region of RGS3 comprises the structural domain for this activity. (NIII IIL,t 1071. DK25295).
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology