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Titolo:
Protein kinase C phosphorylates RGS2 and modulates its capacity for negative regulation of G alpha(11) signaling
Autore:
Cunningham, ML; Waldo, GL; Hollinger, S; Hepler, JR; Harden, TK;
Indirizzi:
Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA Univ NCarolina Chapel Hill NC USA 27599 macol, Chapel Hill, NC 27599 USA Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA Emory Univ Atlanta GA USA 30322 ed, Dept Pharmacol, Atlanta, GA 30322 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 8, volume: 276, anno: 2001,
pagine: 5438 - 5444
SICI:
0021-9258(20010223)276:8<5438:PKCPRA>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
GTPASE-ACTIVATING PROTEINS; STIMULATED PHOSPHOINOSITIDE HYDROLYSIS; TURKEY ERYTHROCYTE-MEMBRANES; HETEROTRIMERIC G-PROTEINS; PHOSPHOLIPASE-C; PHORBOL-ESTER; ALPHA-SUBUNITS; FREE-CALCIUM; INOSITOL TRISPHOSPHATE; GUANINE-NUCLEOTIDES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Harden, TK Univ N Carolina, Sch Med, Dept Pharmacol, CB 7365,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA Univ N Carolina CB 7365,Mary Ellen Jones Bldg Chapel Hill NC USA 27599
Citazione:
M.L. Cunningham et al., "Protein kinase C phosphorylates RGS2 and modulates its capacity for negative regulation of G alpha(11) signaling", J BIOL CHEM, 276(8), 2001, pp. 5438-5444

Abstract

RGS proteins (regulators of G protein signaling) attenuate heterotrimeric G protein signaling by functioning as both GTPase-activating proteins (GAPs) and inhibitors of G protein/effector interaction. RGS2 has been shown to regulate G alpha (q)-mediated inositol lipid signaling. Although purified RGS2 blocks PLC-P activation by the nonhydrolyzable GTP analog guanosine 5'-O-thiophosphate (GTP gammaS), its capacity to regulate inositol lipid signaling under conditions where GTPase-promoted hydrolysis of GTP is operative has not been fully explored. Utilizing the turkey erythrocyte membrane model of inositol lipid signaling, me investigated regulation by RGS2 of both GTP and GTP gammaS-stimulated G alpha (11) signaling. Different inhibitory potencies of RGS2 were observed under conditions assessing its activity as aGAP versus as an effector antagonist; i.e. RGS2 was a 10-20-fold more potent inhibitor of aluminum fluoride and GTP-stimulated PLC-betat activity than of GTP gammaS-promoted PLC-betat activity. We also examined whether RGS2 was regulated by downstream components of the inositol lipid signaling pathway. RGS2 was phosphorylated by PKC in vitro to a stoichiometry of approximately unity by both a mixture of PRC isozymes and individual calcium and phospholipid-dependent PKC isoforms. Moreover, RGS2 was phosphorylated in intact COS7 cells in response to PKC activation by 4 beta -phorbol 12 beta -myristate 13 alpha -acetate and, to a lesser extent, by the P2Y(2) receptor agonist UTP. In vitro phosphorylation of RGS2 by PKC decreased its capacity to attenuate both GTP and GTP gammaS-stimulated PLC-betat activation, with the ex tent of attenuation correlating with the level of RGS2 phosphorylation. A phosphorylation-dependant: inhibition of RGS2 GAP activity was also observed in proteoliposomes reconstituted with purified P2Y(1) receptor and G alpha (q)beta gamma. These results identify for the first time a phosphorylation-induced change in the activity of an RGS protein and suggest a mechanism for potentiation of inositol lipid signaling by PKC.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 09:59:13