The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis

David M. Berman, Tohru Kozasa, Alfred G. Gilman

Research output: Contribution to journalArticle

284 Citations (Scopus)

Abstract

RGS proteins constitute a newly appreciated group of negative regulators of G protein signaling. Discovered by genetic screens in yeast, worms, and other organisms, two mammalian RGS proteins, RGS4 and GAIP, act as GTPase- activating proteins for members of the G(i) family of G protein α subunits. We have purified recombinant RGS4 to homogeneity and demonstrate that it acts catalytically to stimulate GTP hydrolysis by G(i) proteins. Furthermore, RGS4 stabilizes the transition state for GTP hydrolysis, as evidenced by its high affinity for the GDP-AlF 4/ --bound forms of G(oα) and G(iα) and its relatively low affinity for the GTPγS- and GDP-bound forms of these proteins. Consequently, RGS4 is most likely not a downstream effector for activated G(α) subunits. All members of the G(i) subfamily of proteins tested are substrates for RGS4 (including G(tα) and G(zα)); the protein has lower affinity for G(qα), and it does not stimulate the GTPase activity of G(8α) or G(12α).

Original languageEnglish (US)
Pages (from-to)27209-27212
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number44
DOIs
StatePublished - 1996

Fingerprint

GTPase-Activating Proteins
Hydrolysis
Nucleotides
RGS Proteins
Guanosine Triphosphate
Proteins
GTP-Binding Protein Regulators
GTP Phosphohydrolases
Protein Subunits
GTP-Binding Proteins
Yeast
Yeasts
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis. / Berman, David M.; Kozasa, Tohru; Gilman, Alfred G.

In: Journal of Biological Chemistry, Vol. 271, No. 44, 1996, p. 27209-27212.

Research output: Contribution to journalArticle

Berman, David M. ; Kozasa, Tohru ; Gilman, Alfred G. / The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 44. pp. 27209-27212.
@article{173be0e6dac5431d9b4cf0b878d81c46,
title = "The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis",
abstract = "RGS proteins constitute a newly appreciated group of negative regulators of G protein signaling. Discovered by genetic screens in yeast, worms, and other organisms, two mammalian RGS proteins, RGS4 and GAIP, act as GTPase- activating proteins for members of the G(i) family of G protein α subunits. We have purified recombinant RGS4 to homogeneity and demonstrate that it acts catalytically to stimulate GTP hydrolysis by G(i) proteins. Furthermore, RGS4 stabilizes the transition state for GTP hydrolysis, as evidenced by its high affinity for the GDP-AlF 4/ --bound forms of G(oα) and G(iα) and its relatively low affinity for the GTPγS- and GDP-bound forms of these proteins. Consequently, RGS4 is most likely not a downstream effector for activated G(α) subunits. All members of the G(i) subfamily of proteins tested are substrates for RGS4 (including G(tα) and G(zα)); the protein has lower affinity for G(qα), and it does not stimulate the GTPase activity of G(8α) or G(12α).",
author = "Berman, {David M.} and Tohru Kozasa and Gilman, {Alfred G.}",
year = "1996",
doi = "10.1074/jbc.271.44.27209",
language = "English (US)",
volume = "271",
pages = "27209--27212",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "44",

}

TY - JOUR

T1 - The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis

AU - Berman, David M.

AU - Kozasa, Tohru

AU - Gilman, Alfred G.

PY - 1996

Y1 - 1996

N2 - RGS proteins constitute a newly appreciated group of negative regulators of G protein signaling. Discovered by genetic screens in yeast, worms, and other organisms, two mammalian RGS proteins, RGS4 and GAIP, act as GTPase- activating proteins for members of the G(i) family of G protein α subunits. We have purified recombinant RGS4 to homogeneity and demonstrate that it acts catalytically to stimulate GTP hydrolysis by G(i) proteins. Furthermore, RGS4 stabilizes the transition state for GTP hydrolysis, as evidenced by its high affinity for the GDP-AlF 4/ --bound forms of G(oα) and G(iα) and its relatively low affinity for the GTPγS- and GDP-bound forms of these proteins. Consequently, RGS4 is most likely not a downstream effector for activated G(α) subunits. All members of the G(i) subfamily of proteins tested are substrates for RGS4 (including G(tα) and G(zα)); the protein has lower affinity for G(qα), and it does not stimulate the GTPase activity of G(8α) or G(12α).

AB - RGS proteins constitute a newly appreciated group of negative regulators of G protein signaling. Discovered by genetic screens in yeast, worms, and other organisms, two mammalian RGS proteins, RGS4 and GAIP, act as GTPase- activating proteins for members of the G(i) family of G protein α subunits. We have purified recombinant RGS4 to homogeneity and demonstrate that it acts catalytically to stimulate GTP hydrolysis by G(i) proteins. Furthermore, RGS4 stabilizes the transition state for GTP hydrolysis, as evidenced by its high affinity for the GDP-AlF 4/ --bound forms of G(oα) and G(iα) and its relatively low affinity for the GTPγS- and GDP-bound forms of these proteins. Consequently, RGS4 is most likely not a downstream effector for activated G(α) subunits. All members of the G(i) subfamily of proteins tested are substrates for RGS4 (including G(tα) and G(zα)); the protein has lower affinity for G(qα), and it does not stimulate the GTPase activity of G(8α) or G(12α).

UR - http://www.scopus.com/inward/record.url?scp=0029861417&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029861417&partnerID=8YFLogxK

U2 - 10.1074/jbc.271.44.27209

DO - 10.1074/jbc.271.44.27209

M3 - Article

C2 - 8910288

AN - SCOPUS:0029861417

VL - 271

SP - 27209

EP - 27212

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 44

ER -