Regulations Of RGS Proteins On Activity Of Adenylate Cyclases Associated With Opiate Receptors

G protein-mediated signaling is intrinsically kinetic, mainly including 2 key processes i.e. G-protein activation (GTP/GDP exchange) and G-protein deactivation (GTP hydrolysis). Signal amplitude is determined by the balance of the rate of activation and the rate of deactivation. This balance determines the amount of G protein in the activated GTP-bound state and can be modulated by many intracellular factors. GTP/GDP exchange is accelerated by G protein-coupled receptors (GPCRs); GTP hydrolysis is accelerated by GTPase-activating proteins (GAPs). GAPs for heterotrimeric G proteins include some G protein-mediated effectors such as PLC-β1 and recently identified regulators of G protein signaling proteins (RGSs).The first RGS protein Sst2 was originally isolated by genetic analysis of Saccharomyces cerevisiae mutants supersensitive to the cell-cycle-arresting effects of mating pheromone。 Identification of Sst2 as a negative regulator of pheromone signaling, a well-characterized G protein-mediated pathway, afforded us an opportunity to test the functional significance of the Sst2-similar proteins. In addition to Saccharomyces cerevisiae, other homologues to Sst2 exist in some other lower eukaryotes. Egl-10 is a RGS protein from Caenorhabditis elegans, and 12 homologues of Egl-10 exist, as identified through the sequencing consortium. Egl-10 interacts with GOA-1 protein and modulates egg-laying and locomotion behaviors of Caenorhabditis elegans. Another RGS protein fblA was found existing in Aspergillas nidulans and interacting with protein FadA to negatively regulate Aspergillas nidulans conidiophores development. Two RGS proteins have been discovered in Drosophila, dRGS7 and the Loco gene product, homologous to RGS7 and RGS9, and RGS12 and RGS14, respectively. Furthermore, using a variety of cloning strategies, no less than 30 mammalian RGS homologues to the yeast and invertebrate proteins have been...