title: Activation of transducin guanosine triphosphatase by two proteins of the RGS family.
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 alpha-subunits, including the photoreceptor G protein, transducin. In photoreceptor cells transducin GTPase is known to be substantially accelerated by the coordinated action of the gamma-subunit of its effector enzyme, cGMP phosphodiesterase (PDE gamma), 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 G alpha 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 PDE gamma for activating transducin. Rather, PDE gamma causes a partial reversal of transducin GTPase activation by RGS proteins. The effect of PDE gamma is based on a decreased apparent affinity of RGS for the alpha-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.
authors.affiliation: Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston 02114, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Nekrasova
authors.forename: D M
authors.initials: DM
authors.lastname: Berman
authors.forename: R R
authors.initials: RR
authors.lastname: Rustandi
authors.forename: H E
authors.initials: HE
authors.lastname: Hamm
authors.forename: A G
authors.initials: AG
authors.lastname: Gilman
authors.forename: V Y
authors.initials: VY
authors.lastname: Arshavsky
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D020710:RGS Proteins; D012374:Rod Cell Outer Segment / Q000201:enzymology
chemical_list: D010750:Phosphoproteins; D011506:Proteins; D020710:RGS Proteins; C097187:regulator of G-protein signalling 19; C098799:RGS4 protein; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D020558:GTP Phosphohydrolases