Evolution of the regulators of G-protein signaling multigene family in mouse and human. Sierra DA et al. (2002) The regulators of G-protein signaling (RGS) proteins are important regulatory and structural components of G-protein coupled receptor complexes. RGS proteins are GTPase activating proteins (GAPs) of Gi-and Gq-class Galpha proteins, and thereby accelerate signaling kinetics and termination. Here, we mapped the chromosomal positions of all 21 Rgs genes in mouse, and determined human RGS gene structures using genomic sequence from partially assembled bacterial artificial chromosomes (BACs) and Celera fragments. In mice and humans, 18 of 21 RGS genes are either tandemly duplicated or tightly linked to genes encoding other components of G-protein signaling pathways, including Galpha, Ggamma, receptors (GPCR), and receptor kinases (GPRK). A phylogenetic tree revealed seven RGS gene subfamilies in the yeast and metazoan genomes that have been sequenced. We propose that similar systematic analyses of all multigene families from human and other mammalian genomes will help complete the assembly and annotation of the human genome sequence.//////////////////
Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family. Druey KM et al. (1996) A general property of signal transduction pathways is that prolonged stimulation decreases responsiveness, a phenomenon termed desensitization. Yeast cells stimulated with mating pheromone activate a heterotrimeric G-protein-linked, MAP-kinase-dependent signalling pathway that induces G1-phase cell-cycle arrest and morphological differentiation (reviewed in refs 1, 2). Eventually the cells desensitize to pheromone and resume growth. Genetic studies have demonstrated the relative importance of a desensitization mechanism that uses the SST2 gene product, Sst2p. Here we identify a mammalian gene family termed RGS (for regulator of G-protein signalling) that encodes structural and functional homologues of Sst2p. Introduction of RGS family members into yeast blunts signal transduction through the pheromone-response pathway. Like SST2 (refs 8-10), they negatively regulate this pathway at a point upstream or at the level of the G protein. The RGS family members also markedly impair MAP kinase activation by mammalian G-protein-linked receptors, indicating the existence and importance of an SST2-like desensitization mechanism in mammalian cells.//////////////////
NCBI Summary:
The protein encoded by this gene belongs to the RGS (regulator of G protein signaling) family. Members of the RGS family act as GTPase-activating proteins on the alpha subunits of heterotrimeric, signal-transducing G proteins. This protein inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Alternative splicing occurs at this locus and four transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Nov 2013]
General function
Intracellular signaling cascade
Comment
Cellular localization
Cytoplasmic
Comment
Ovarian function
Comment
Expression regulated by
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Ovarian localization
Cumulus, Granulosa
Comment
Differential expression of poliovirus receptor, regulator of G-protein signaling 11 and erythrocyte protein band 4.1-like 3 in human granulosa cells during follicular growth and maturation. Barzilay E 2014 et al.
Abstract Poliovirus receptor (PVR), regulator of G-protein signaling-11 (RGS11), and erythrocyte protein band-4.1-like 3 (EPB41L3) have been proposed to function in follicular maturation in mouse models. We have examined their expression in human mural (mGCs) and cumulus granulosa cells (CCs). Expression of PVR and RGS11 in mGCs decreased in medium-sized follicles compared to small follicles of IVM cycles and increased again in large follicles. Luteinization caused decreased expression of both PVR and RGS11. In vitro incubation of mGCs with progesterone-rich conditioned media decreased expression of RGS11 without affecting PVR levels. Inhibition of progesterone signaling enhanced expression of both RGS11 and PVR. Expression in CCs was examined by means of global transcriptome sequencing analysis RGS11 and EPB41L3 increased in CCs during follicular maturation while PVR levels did not change. In conclusion, during human follicular maturation there are significant changes in expression of PVR, RGS11 and EPB41L3, possibly regulated by progesterone.
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Expression Patterns of Poliovirus Receptor, Erythrocyte Protein Band 4.1-Like 3, Regulator of G-Protein Signaling 11 and Oxytocin Receptor in Mouse Ovarian Cells During Follicle Growth and Early Luteinization In Vitro and In Vivo. Segers I et al. Poliovirus receptor (Pvr), erythrocyte protein band 4.1-like 3 (Epb4.1l3), regulator of G-protein signaling 11 (Rgs11), and oxytocin receptor (Oxtr) expression were quantified in in vitro and in vivo grown mouse follicles. The expression of all genes was increased during antral growth in in vitro grown cumulus cells, while only Rgs11 and Oxtr were increased and Pvr and Epb4.1l3 were decreased in in vivo grown cumulus cells. In vivo mural granulosa cells showed the highest expression of Pvr, Rgs11, and Oxtr. The in vitro granulosa+theca compartment responded to hCG during early luteinization by either an up regulation (Pvr, Oxtr) or down regulation (Epb41l3, Rgs11). Oocytes expressed Epb4.1l3, not Rgs11, and Pvr only in in vitro grown oocytes. Translation into protein was confirmed for Epb4.1l3 in in vitro grown follicles and in vivo grown cumulus oocyte complexes. Protein 4.1B was present during antral growth in cumulus, granulosa cells and oocytes. Hypothetical functions of Epb4.1l3 and Pvr involve cell adhesion regulation and Rgs11 could be cAMP production in the follicle. Oxtr is known to be important during and after the ovulatory stimulus, but as in bovine, was also regulated during folliculogenesis. High expression of Pvr and Epb4.1l3 with culture duration in cumulus cells might mark the inappropriate differentiation into a mural granulosa-like cell type and function as negative follicle development marker. Rgs11 and Oxtr are both in vivo and in vitro up regulated in cumulus cells during antral follicle growth and might be considered positive markers for follicle development.