RGS17/RGSZ2, a Novel Regulator of Gi/o, Gz, and Gq Signaling

To identify novel regulators of Gαo, the most abundant G-protein in brain, we used yeast two-hybrid screening with constitutively active Gαo as bait and identified a new regulator of G-protein signaling (RGS) protein, RGS17 (RGSZ2), as a novel human member of the RZ (or A) subfamily of RGS proteins. RGS17 contains an amino-terminal cysteine-rich motif and a carboxyl-terminal RGS domain with highest homology to hRGSZ1- and hRGS-Gα-interacting protein. RGS17 RNA was strongly expressed as multiple species in cerebellum and other brain regions. The interactions between hRGS17 and active forms of Gαi1–3, Gαo, Gαz, or Gαq but not Gαs were detected by yeast two-hybrid assay, in vitro pull-down assay, and co-immunoprecipitation studies. Recombinant RGS17 acted as a GTPase-activating protein (GAP) on free Gαi2 and Gαo under pre-steady-state conditions, and on M2-muscarinic receptor-activated Gαi1, Gαi2, Gαi3, Gαz, and Gαo in steady-state GTPase assays in vitro. Unlike RGSZ1, which is highly selective for Gz, RGS17 exhibited limited selectivity for Go among Gi/Go proteins. All RZ family members reduced dopamine-D2/Gαi-mediated inhibition of cAMP formation and abolished thyrotropin-releasing hormone receptor/Gαq-mediated calcium mobilization. RGS17 is a new RZ member that preferentially inhibits receptor signaling via Gi/o, Gz, and Gq over Gs to enhance cAMP-dependent signaling and inhibit calcium signaling. Differences observed between in vitro GAP assays and whole-cell signaling suggest additional determinants of the G-protein specificity of RGS GAP effects that could include receptors and effectors. To identify novel regulators of Gαo, the most abundant G-protein in brain, we used yeast two-hybrid screening with constitutively active Gαo as bait and identified a new regulator of G-protein signaling (RGS) protein, RGS17 (RGSZ2), as a novel human member of the RZ (or A) subfamily of RGS proteins. RGS17 contains an amino-terminal cysteine-rich motif and a carboxyl-terminal RGS domain with highest homology to hRGSZ1- and hRGS-Gα-interacting protein. RGS17 RNA was strongly expressed as multiple species in cerebellum and other brain regions. The interactions between hRGS17 and active forms of Gαi1–3, Gαo, Gαz, or Gαq but not Gαs were detected by yeast two-hybrid assay, in vitro pull-down assay, and co-immunoprecipitation studies. Recombinant RGS17 acted as a GTPase-activating protein (GAP) on free Gαi2 and Gαo under pre-steady-state conditions, and on M2-muscarinic receptor-activated Gαi1, Gαi2, Gαi3, Gαz, and Gαo in steady-state GTPase assays in vitro. Unlike RGSZ1, which is highly selective for Gz, RGS17 exhibited limited selectivity for Go among Gi/Go proteins. All RZ family members reduced dopamine-D2/Gαi-mediated inhibition of cAMP formation and abolished thyrotropin-releasing hormone receptor/Gαq-mediated calcium mobilization. RGS17 is a new RZ member that preferentially inhibits receptor signaling via Gi/o, Gz, and Gq over Gs to enhance cAMP-dependent signaling and inhibit calcium signaling. Differences observed between in vitro GAP assays and whole-cell signaling suggest additional determinants of the G-protein specificity of RGS GAP effects that could include receptors and effectors. Regulators of G-protein signaling (RGS) 1The abbreviations used are: RGS, regulator of G-protein signaling; GAP, GTPase activating protein; PMSF, phenylmethylsulfonyl fluoride; TRHR1, rat thyrotropin-releasing hormone receptor; RACE, rapid amplification of cDNA ends; β-ME, β-mercaptoethanol; Ni-NTA, nickel-nitrilotriacetic acid; PTX, pertussis toxin; GST, glutathione S-transferase; GS, Gly → Ser mutation; QL, Gln → Leu mutation; RC, Arg → Cys mutation; TRH, thyrotropin-releasing hormone. proteins accelerate the intrinsic GTPase activity of heterotrimeric G-protein Gα subunits. All RGS proteins contain a conserved RGS core domain, which is an interaction site for the Gα subunits (1Burchett S.A. J. Neurochem. 2000; 75: 1335-1351Crossref PubMed Scopus (98) Google Scholar, 2De Vries L. Zheng B. Fischer T. Elenko E. Farquhar M.G. Annu. Rev. Pharmacol. Toxicol. 2000; 40: 235-271Crossref PubMed Scopus (508) Google Scholar, 3Ross E.M. Wilkie T.M. Annu. Rev. Biochem. 2000; 69: 795-827Crossref PubMed Scopus (929) Google Scholar). There are more than 30 human RGS or RGS-like proteins that are classified into six subfamilies based upon their sequence homology and that have conserved functional and targeting domains outside of the RGS domain. For instance, a membrane-targeting domain immediately proximal to the RGS core domain directs small RGS proteins such as RGS1–5 and -16 to the cell membrane (4Heximer S. Lim H. Bernard J. Blumer K. J. Biol. Chem. 2001; 276: 14195-14203Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar). Putative nuclear localization signals have been found within (5Chatterjee T.K. Fisher R.A. J. Biol. Chem. 2000; 275: 24013-24021Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar) and also outside of the RGS core domain (6Dulin N.O. Pratt P. Tiruppathi C. Niu J. Voyno-Yasenetskaya T. Dunn M.J. J. Biol. Chem. 2000; 275: 21317-21323Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar), and this may direct certain RGS subtypes to the nucleus (7Zmijewski J.W. Song L. Harkins L. Cobbs C.S. Jope R.S. Biochim. Biophys. Acta. 2001; 1541: 201-211Crossref PubMed Scopus (25) Google Scholar, 8Burchett S.A. J. Neurochem. 2003; 87: 551-559Crossref PubMed Scopus (44) Google Scholar). RZ family members, such as RGSZ1 and RGS-Gα-interacting protein (GAIP), contain a cysteine-rich motif that may serve as a palmitoylation site for membrane association (9Tu Y. Popov S. Slaughter C. Ross E.M. J. Biol. Chem. 1999; 274: 38260-38267Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, 10De Vries L. Elenko E. Hubler L. Jones T. Farquhar M.G. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 15203-15208Crossref PubMed Scopus (156) Google Scholar). A more recent study showed that RZ family members also serve as adapter proteins for Gα subunit degradation (11Fischer T. De Vries L. Meerloo T. Farquhar M.G. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 8270-8275Crossref PubMed Scopus (65) Google Scholar). The cysteine-rich motif interacts with the leucine-rich region of GAIP-interacting protein N terminus, an E3 ubiquitin ligase responsible for Gαi3 degradation. Recently RGSZ1 and RGS6 have been shown to associate with SCG-10, a protein involved in neuronal differentiation (12Nixon A.B. Grenningloh G. Casey P.J. J. Biol. Chem. 2002; 277: 18127-18133Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 13Liu Z. Chatterjee T.K. Fisher R.A. J. Biol. Chem. 2002; 24: 30261-30271Google Scholar), and the Gz GTPase-activating protein (GAP) effects of RGSZ1 (and other RGS proteins) were found to be negatively regulated by synapsin-1a (14Tu Y. Nayak S.K. Woodson J. Ross E.M. J. Biol. Chem. 2003; 278: 52273-52281Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar). Thus, RZ proteins may play diverse and important roles in the regulation of signaling and cytoskeletal events in the brain. G-protein specificity of RGS proteins has been investigated in various studies. Some RGS proteins display a preference for Gα sub-families (15Posner B.A. Mukhopadhyay S. Tesmer J.J. Gilman A.G. Ross E.M. Biochemistry. 1999; 38: 7773-7779Crossref PubMed Scopus (68) Google Scholar), with the majority regulating Gαi/o and a subset of these also acting on Gαq (16Berman D.M. Gilman A.G. J. Biol. Chem. 1998; 273: 1269-1272Abstract Full Text Full Text PDF PubMed Scopus (445) Google Scholar, 17Mukhopadhyay S. Ross E.M. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: PubMed Scopus Google Scholar, Popov S. Mukhopadhyay S. P. J. Fisher Ross E.M. S. Wilkie T.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, P. Pharmacol. 2002; PubMed Scopus Google Scholar). RGS members are more selective regulators of Gα subunits. For instance, has a preference for subunits T. M.J. Gilman A.G. G. 1998; PubMed Scopus Google Scholar). RGSZ1 to be selective for J. A. Y. T. Ross E.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, A. Casey P.J. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar), has been shown to with and negatively subunits Y. G. J.J. B. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). a of family RGS proteins a preference in the regulation of proteins than an specificity for J. T.K. J. Biol. Chem. 2003; 278: Full Text Full Text PDF PubMed Scopus Google Scholar). The most abundant G-protein expressed in the brain is of Gαo are by of and is of the for the Gαo To identify regulators or we human brain cDNA for proteins a yeast two-hybrid with constitutively active as RGS17 was identified among a of RGS17 contains a cysteine-rich N by the highly conserved RGS domain, and is most to RGSZ1 and other RZ family have the G-protein specificity of RGS17 by GAP interaction and functional that as as RGSZ1, negatively the of Gz, and Gαq subunits. active rat Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar) cDNA was into for two-hybrid and for were into and or All and were of RGS17 or Gα subunits into The Gly → Ser of Gα subunit were the All were by RGSZ1 and in were the and for in were in For the of proteins for GTPase for Gαi2, and Gαo were by for and Gαi3 were by of for Gαo and Gαz, were and Casey were as P. Pharmacol. 2002; PubMed Scopus Google Scholar). thyrotropin-releasing hormone receptor cDNA was by H. was used as a bait to of a human brain cDNA in yeast the A. A. PubMed Scopus Google Scholar). 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Pharmacol. 2002; PubMed Scopus Google Scholar). was as J. A. Y. T. Ross E.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar) and in the which exhibited GAP activity with that of For of Gαi2 and Gαo E. in A β-ME, and were was and the were on for 30 by the of in the of for The was for 30 and the of the was to with A with and of and was in the for and a with 30 of A with and and with 30 of A and with and G-protein was with the The was by or a of PMSF, and The protein was and GTPase a of were with the Gαi1, Gαi2, Gαi3, Gαo, or Gαz, and of cell were as P. Pharmacol. 2002; PubMed Scopus Google Scholar) and in a PMSF, and The steady-state of by was in the and of RGS proteins as P. Pharmacol. 2002; PubMed Scopus Google Scholar). PMSF, and free were 30 for with or and cell The was by of in and of in the was by The membrane GTPase was by of to the and GTPase activity was as P. Pharmacol. 2002; PubMed Scopus Google Scholar). GTPase of by Gαi2 and Gαo was as Blumer 1996; PubMed Scopus Google Scholar) with Gαi2 or Gαo was with for and on a of was by the of to the and of RGS protein. were various by of with The was and the in the was by were by to a and was with or with and in The were for and the were with on for The was with in and on an The was a membrane and in in The membrane was with or and The membrane was with and to was with into by the S. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). the were in and on for 30 to The cell was for The of and subunits were with of The was with in for to the proteins. The were on an and by cAMP were with and receptor with or or rat Gα subunits as S. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). was to the for were into the were with for and in with in the The was were for 30 and the was for cAMP S. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). in were with of cDNA J. Jones C. Y. P. Scopus Google Scholar) and of or by Pharmacol. PubMed Scopus Google Scholar, P. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). the were and in and with in for 30 with The were with in of and to were to the a identify novel we a human brain cDNA with constitutively active for proteins a yeast two-hybrid human RGS17 was cDNA sequence a protein of with a of RGS17 contains a core RGS domain and a motif the There are six and hRGS17 to the rat RGS17 with the and to that these are species of RGS17 has the highest homology to RZ subfamily RGS proteins with of and with and that RGS17 is a new member of the RZ of that RGS17 is expressed in we the of RGS17 in human by RGS17 were found in various brain with and the the RGS17 was expressed most in the cerebellum the species was more abundant in and and The multiple RGS17 in brain may in a of human the RGS17 was detected not The of this is to the RGSZ1 J. A. Y. T. Ross E.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, A. Casey P.J. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar) and the Vries L. A. Farquhar M.G. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). Thus, multiple RGS17 are expressed in the cerebellum and other brain regions. we detected RGS17 RNA species in brain, we of a human brain cDNA to for a and was to and than the cDNA Thus, the human RGS17 RNA in brain to have the and in RNA may be to regions. Gα of RGS17 direct interactions between RGS17 and in vitro pull-down assays were proteins the of to the but not GST, was with a direct interaction between RGS17 and Gαo were proteins expressed in with a interaction of with To G-protein interactions between RGS17 and Gα subtypes and their constitutively active were in multiple RGS17 more strongly with the Gln → Leu and than with their with the of Gαo and Gαi3 interaction was detected between RGS17 and or in assays not Thus, RGS17 is selective for Gαi/o and proteins and preferentially the A of the and Gαo subunits their interaction with RGS proteins J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). The of this site in RGS17 interaction with was the yeast interaction The interaction between RGS17 and constitutively active Gαo Arg → Cys and proteins was abolished upon of the were observed for the interaction of with these showed in interaction with or the selectivity of the for RGS The interaction specificity was by co-immunoprecipitation and or or were in The of Gαi2, Gαi3, and Gαq with but the that the interaction with RGS17 determinants of Gα subunits. G-protein of RGS17 GAP of RGS17 was steady-state and GAP RGS17 the which was by members of the family under GTPase observed of activity were with Gαi2 than with Gαo RGS17 or the of of these free RGS17 an GAP on these in heterotrimeric with receptor in assays RGS17 GAP activity a between and in these a The GAP activity of RGS17 was also observed in the receptor Gαz, Gαi1, or Gαi3 RGS17 and RGSZ1 GAP effects on are by functional in such in GTPase activity could not be in these in vitro assays not activity of RGS17 on receptor-activated Gαi2 and RGS17 was the on the for on the of in receptor heterotrimeric Go or of and of membrane protein with Gαo and The GAP effects were by observed in the of the but in the of RGS of RGS17 and RGSZ1 GAP The of by Gαi2 and Gαo was as in in the of RGS protein or in the of the of RGS17 or steady-state GTPase activity was in the of RGS proteins in the receptor heterotrimeric Gαi1, Gαi2, Gαi3, Gαo, or in RGS GAP activity was as the of over that observed with the and with or RGS17 or RGSZ1 were as the of observed in the of a activating of GTPase signals of membrane for the various in the of were and to RGSZ1 GTPase of Gαo and than other RGS17 was active on Gα subunits over a with a preference for Gαo and the GAP activity of RGS17 in steady-state assays was found to be than RGSZ1 activity but than that of The for this with is RGS17 is a GAP than under pre-steady-state conditions, we found that the in with to their interactions with free in pre-steady-state GAP assays not Thus, to be the of RGS17 in the to the of steady-state and pre-steady-state GAP we RGS17 to RGSZ1, a member of the RGS protein subfamily RGS proteins in the of by Gαo and Gαi2, RGS17 the of For with Gαi2 RGS17 the of to the of RGSZ1 to The between RGS17 and RGSZ1 was more in steady-state assays Unlike the of GAP activity of RGS17 on and Gz, an of RGSZ1 or RGSZ1 the of by free Gα proteins by an of the of RGSZ1 to to an over GTPase RGSZ1 activity could not be of in protein to RGSZ1 GAP effects in the receptor the of RGSZ1 was that of RGS17 with and was with Gz, the selectivity of RGSZ1 for Gz in the of of RGS17 on the functional activity and specificity of RGS17 in activity to inhibit inhibition of cAMP formation was which were with receptors cAMP and receptors inhibit S. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar), in the or of were with to receptors or with to but receptor signaling. The in cAMP between the the of cAMP formation was reduced by upon of receptors The of was reduced by of of which was detected with was of cAMP of of of which is with the observed of interaction between RGS17 and The G-protein specificity of RGS17 and other RZ family members on or inhibition of cAMP was by with or subunits the of Gα subunits the by of or RGSZ1 with or reduced the by Gα with the of RGS17 on Gαz, upon which the was not this was not to a preference of RGSZ1 for Gαz, RGSZ1 Gαz, as shown by the in vitro GAP A. Casey P.J. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). To the of the interaction between RGS17 and we the of RZ family members on calcium in with and or RGSZ1 and calcium signaling. of thyrotropin-releasing hormone an in was observed of PubMed Scopus (25) Google Scholar). by was by RZ member the of in was in not that RGS proteins not the receptor that RZ family members as for signaling may serve as in this a RZ on interaction with Gαo, we have identified a novel RGS protein with homology to RZ or A subfamily members Vries L. Zheng B. Fischer T. Elenko E. Farquhar M.G. Annu. Rev. Pharmacol. Toxicol. 2000; 40: 235-271Crossref PubMed Scopus (508) Google Scholar, 3Ross E.M. Wilkie T.M. Annu. Rev. Biochem. 2000; 69: 795-827Crossref PubMed Scopus (929) Google Scholar). that RGS17 is as RNA with multiple species in brain the RGSZ1 is expressed in the brain J. A. Y. T. Ross E.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, A. Casey P.J. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, S.A. J. Ross E.M. 2001; PubMed Scopus Google Scholar). is that of the protein which is highly expressed in and expressed in brain Vries L. A. Farquhar M.G. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). The human RGS17 more than and contains K. P. S.A. G. G. Wilkie T.M. 2002; PubMed Scopus Google Scholar), and could be to to multiple RNA the are in to a of RGSZ1 S.A. J. Ross E.M. 2001; PubMed Scopus Google Scholar). RGS17 have been identified in human and rat and All have the with a or of the to of the in protein A. PubMed Scopus Google Scholar). The of the that RGS17 RNA not and we found for between the and the that RGS17 not contain an RGS17 for a of RGSZ1 with an domain that is expressed in S.A. J. Ross E.M. 2001; PubMed Scopus Google Scholar), the RZ subfamily of RGS proteins with and The motif is highly conserved and as a protein interaction site (11Fischer T. De Vries L. Meerloo T. Farquhar M.G. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 8270-8275Crossref PubMed Scopus (65) Google Scholar). The is to direct localization of and RGSZ1 to such as the and J. A. Y. T. Ross E.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, K. G. J. 1999; 276: PubMed Google Scholar). of the domain of RGSZ1 nuclear that the domain of RGS17 may direct localization (5Chatterjee T.K. Fisher R.A. J. Biol. Chem. 2000; 275: 24013-24021Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar), by of protein the of RZ members, were shown to with GAIP-interacting protein N terminus, a novel protein that to enhance the degradation of RZ proteins (11Fischer T. De Vries L. Meerloo T. Farquhar M.G. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 8270-8275Crossref PubMed Scopus (65) Google Scholar). is a leucine-rich nuclear sequence (5Chatterjee T.K. Fisher R.A. J. Biol. Chem. 2000; 275: 24013-24021Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar) in the RGS domain of RGS17 which that of RGS17 to the may be be to identify the roles of these domains in RGS17 G-protein of RZ with members of the subfamily and and Gαq in yeast and in vitro and co-immunoprecipitation but interaction with Gαs and The observed interactions were in functional effects RGS17 exhibited GAP activity Gαo, and and signaling via Gαi2, Gαi3, and yeast assays suggest RGS17 selectivity were to of RGS17 on inhibition of cAMP Gαo to to inhibition of cAMP in not Gαo inhibits that is in J. Pharmacol. 1999; PubMed Scopus Google Scholar), which the of Gαo signaling in these in of receptor-activated Gαo were observed with the of RGS17 GAP activity was the for RGS17 also exhibited a GAP on receptor-activated a on the regulation of cAMP by this RGS effects were more to with Gαz, which is with to other proteins J. A. Y. T. Ross E.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar) and to effects on cAMP suggest that RGS17 is a GAP for members of the protein subfamily of heterotrimeric with selectivity among and that this GAP activity their signaling. we were to RGS17 GAP activity on to Gαq and inhibit signaling. may between the assays in may to a of signaling The that RGS17 may as an is by recent that the inhibition by RGS proteins of (and calcium not RGS GAP activity T. U. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. P. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). RGS17 is most to RGSZ1 J. A. Y. T. Ross E.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, A. Casey P.J. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). to RGSZ1 and a of signaling to RGSZ1 to be selective for Gz, which is with GTPase assays in the with J. A. Y. T. Ross E.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar), the of free RGSZ1 on receptor-activated heterotrimeric was with effects on Gα proteins. RGSZ1 is to be a selective GAP for Gαz, as by GAP assays on free J. A. Y. T. Ross E.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, A. Casey P.J. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). RGSZ1 in the study also showed an or on subunits with in regulating inhibition of Y. G. J.J. B. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar) found that RGSZ1 interacts with and GTPase GAP effects on Gαi2 and Gαo J. A. Y. T. Ross E.M. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, A. Casey P.J. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). The suggest that the between may have been The more recent study Y. G. J.J. B. J. Biol. 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Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). steady-state RGSZ1 GAP effects on Gαi1, Gαi2, Gαi3, and the suggest that RGSZ1 is a selective GAP and a of signals via members of the between effects of RGS17 and RGSZ1 on and suggest the that the specificity of RGS proteins to enhance GTPase activity in vitro may not to their to signaling in RGS17 as an of RZ family members are to inhibition of cAMP novel that RGS17 also interacts with Gαq and that RGS17 and other RZ members receptor/Gαq-mediated calcium a for these proteins as of signaling. Thus, RGS17 negatively of the receptor and signaling. the and in receptor signaling inhibits the of calcium is J. Biol. Chem. Full Text PDF PubMed Google Scholar, 2002; PubMed Scopus Google Scholar). of RGS17 in a to and in The of RGS17 but is that play a more important in of RZ family

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