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).
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U2 - 10.1074/jbc.271.44.27209
DO - 10.1074/jbc.271.44.27209
M3 - Article
C2 - 8910288
AN - SCOPUS:0029861417
SN - 0021-9258
VL - 271
SP - 27209
EP - 27212
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 44
ER -