Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2002 Jul 23;9915:10138-43. doi: 10.1073/pnas.152085999.
Show Gene links
Show Anatomy links
Alternative splicing of RGS8 gene determines inhibitory function of receptor type-specific Gq signaling.
Saitoh O
,
Murata Y
,
Odagiri M
,
Itoh M
,
Itoh H
,
Misaka T
,
Kubo Y
.
???displayArticle.abstract???
The regulators of G protein signaling (RGS) proteins modulate heterotrimeric G protein signaling. RGS8 is a brain-specific RGS protein of 180 aa. Here we identified a short isoform of RGS8, RGS8S, that arises by alternative splicing. RGS8S cDNA encodes a N terminus of 7 aa instead of amino acids 1-9 of RGS8 and 10-180 of RGS8. The subcellular distribution of RGS8 and RGS8S did not differ significantly in transfected cells. RGS8S accelerated, not as efficiently as RGS8, the turning on and off of Gi/o-mediated modulation of G protein-gated inwardly rectifying K(+) channels in Xenopus oocytes. We next examined the effects of RGS8 and RGS8S on Gq-mediated signaling. RGS8 decreased the amplitude of the response upon activation of m1 muscarinic or substance P receptors, but did not remarkably inhibit signaling from m3 muscarinic receptors. In contrast, RGS8S showed much less inhibition of the response of either of these Gq-coupled receptors. By quantitative analysis of the inhibitory effect and the protein expression level, we confirmed that the difference of inhibitory effect is caused by both the qualitative difference between RGS8 and RGS8S and the quantitative difference of the protein expression level. We also confirmed that the receptor-type specificity of inhibition is not caused by the difference of the expression level of the receptors. In summary, we showed that 9 aa in the N terminus of RGS8 contribute to the function to inhibit Gq-coupled signaling in a receptor type-specific manner and that the regulatory function of RGS8S is especially diminished on Gq-coupled responses.
Berman,
Mammalian RGS proteins: barbarians at the gate.
1998, Pubmed
Berman,
Mammalian RGS proteins: barbarians at the gate.
1998,
Pubmed
Berridge,
Inositol trisphosphate and calcium signalling.
1993,
Pubmed
Burchett,
Regulators of G protein signaling: a bestiary of modular protein binding domains.
2000,
Pubmed
Chatterjee,
A truncated form of RGS3 negatively regulates G protein-coupled receptor stimulation of adenylyl cyclase and phosphoinositide phospholipase C.
1997,
Pubmed
Chuang,
Evidence that the nucleotide exchange and hydrolysis cycle of G proteins causes acute desensitization of G-protein gated inward rectifier K+ channels.
1998,
Pubmed
Dohlman,
RGS proteins and signaling by heterotrimeric G proteins.
1997,
Pubmed
Doupnik,
RGS proteins reconstitute the rapid gating kinetics of gbetagamma-activated inwardly rectifying K+ channels.
1997,
Pubmed
,
Xenbase
Druey,
Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family.
1996,
Pubmed
Dulin,
RGS3 inhibits G protein-mediated signaling via translocation to the membrane and binding to Galpha11.
1999,
Pubmed
Dulin,
Regulator of G protein signaling RGS3T is localized to the nucleus and induces apoptosis.
2000,
Pubmed
Itoh,
RGS8 protein is distributed in dendrites and cell body of cerebellar Purkinje cell.
2001,
Pubmed
Koelle,
EGL-10 regulates G protein signaling in the C. elegans nervous system and shares a conserved domain with many mammalian proteins.
1996,
Pubmed
Kurjan,
The pheromone response pathway in Saccharomyces cerevisiae.
1993,
Pubmed
Niwa,
Efficient selection for high-expression transfectants with a novel eukaryotic vector.
1991,
Pubmed
Nomoto,
Distribution of RGS4 mRNA in mouse brain shown by in situ hybridization.
1997,
Pubmed
Rhee,
Regulation of phosphoinositide-specific phospholipase C isozymes.
1997,
Pubmed
Saitoh,
RGS8 accelerates G-protein-mediated modulation of K+ currents.
1997,
Pubmed
,
Xenbase
Saitoh,
Molecular cloning and characterization of Xenopus RGS5.
2000,
Pubmed
,
Xenbase
Saitoh,
Regulator of G protein signaling 8 (RGS8) requires its NH2 terminus for subcellular localization and acute desensitization of G protein-gated K+ channels.
2001,
Pubmed
Tytgat,
Reversal of rectification and alteration of selectivity and pharmacology in a mammalian Kv1.1 potassium channel by deletion of domains S1 to S4.
1994,
Pubmed
,
Xenbase
Zeng,
The N-terminal domain of RGS4 confers receptor-selective inhibition of G protein signaling.
1998,
Pubmed
Zerangue,
G-protein signaling: fine-tuning signaling kinetics.
1998,
Pubmed