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Activation of Transducin Guanosine Triphosphatase by Two Proteins of the RGS Family

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Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235, and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611
Cite this: Biochemistry 1997, 36, 25, 7638–7643
Publication Date (Web):June 24, 1997
https://doi.org/10.1021/bi970427r
Copyright © 1997 American Chemical Society

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    Abstract

    RGS proteins (regulators of G protein signaling) constitute a newly appreciated group of negative regulators of G protein signaling. Several members of this group stimulate the guanosine triphosphatase (GTPase) activity of various G protein α-subunits, including the photoreceptor G protein, transducin. In photoreceptor cells transducin GTPase is known to be substantially accelerated by the coordinated action of the γ-subunit of its effector enzyme, cGMP phosphodiesterase (PDEγ), and another yet unidentified membrane-associated protein factor. Here we test the possibility that this factor belongs to the RGS family of GTPase stimulators. We report a detailed kinetic analysis of transducin GTPase activation by two members of the RGS family, RGS4 and Gα interacting protein (GAIP). RGS4, being at least 5-fold more potent than GAIP, stimulates the rate of transducin GTPase by 2 orders of magnitude. Neither RGS4 nor GAIP requires PDEγ for activating transducin. Rather, PDEγ causes a partial reversal of transducin GTPase activation by RGS proteins. The effect of PDEγ is based on a decreased apparent affinity of RGS for the α-subunit of transducin. Our observations indicate that GTPase activity of transducin can be activated by at least two distinct mechanisms, one based on the action of RGS proteins alone and another involving the cooperative action of the effector enzyme and another protein.

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     This work was supported by NIH Grants EY 10336 to V.Y.A. and GM 34497 to A.G.G. V.Y.A. is a recipient of the Jules and Doris Stein Professorship from Research to Prevent Blindness Inc. A.G.G. is supported by the Raymond and Ellen Willie Distinguished Chair of Molecular Neuropharmacology.

     Harvard Medical School and Massachusetts Eye and Ear Infirmary.

    §

     The University of Texas Southwestern Medical Center.

     Northwestern University Medical School.

    *

     Address correspondence to this author at Howe Laboratory of Ophthalmology, Harvard Medical School/ MEEI, 243 Charles St., Boston, MA 02114. Tel (617) 573-4371; FAX (617) 573-4290; email [email protected].

     Abstract published in Advance ACS Abstracts, June 1, 1997.

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