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(Received for publication, August 28, 1996)
From the Department of Pharmacology, The University of Texas
Southwestern Medical Center, Dallas, Texas 75235
RGS proteins constitute a newly appreciated group
of negative
Volume 271, Number 44,
Issue of November 1, 1996
pp. 27209-27212
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
egulators of 
protein
ignaling. 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 Gi family of
G protein 
subunits. We have purified recombinant RGS4 to
homogeneity and demonstrate that it acts catalytically to stimulate GTP
hydrolysis by Gi proteins. Furthermore, RGS4 stabilizes the
transition state for GTP hydrolysis, as evidenced by its high affinity
for the
GDP-AlF4
-bound
forms of Go
and Gi and its relatively low
affinity for the GTP
S- and GDP-bound forms of these proteins.
Consequently, RGS4 is most likely not a downstream effector for
activated G subunits. All members of the Gi
subfamily of proteins tested are substrates for RGS4 (including
Gt and Gz); the protein has lower
affinity for Gq, and it does not stimulate the GTPase
activity of Gs or G12.
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