Inhibition of brain Gz GAP and other RGS proteins by palmitoylation of G protein alpha subunits.
Palmitoylation of the alpha subunit of the guanine nucleotide-binding protein Gz inhibited by more than 90 percent its response to the guanosine triphosphatase (GTPase)-accelerating activity of Gz GAP, a Gz-selective member of the regulators of G-protein signaling (RGS) protein family of GTPase-activating proteins (GAPs). Palmitoylation both decreased the affinity of Gz GAP for the GTP-bound form of Galphaz by at least 90 percent and decreased the maximum rate of GTP hydrolysis. Inhibition was reversed by removal of the palmitoyl group by dithiothreitol. Palmitoylation of Galphaz also inhibited its response to the GAP activity of Galpha-interacting protein (GAIP), another RGS protein, and palmitoylation of Galphai1 inhibited its response to RGS4. The extent of inhibition of Gz GAP, GAIP, RGS4, and RGS10 correlated roughly with their intrinsic GAP activities for the Galpha target used in the assay. Reversible palmitoylation is thus a major determinant of Gz deactivation after its stimulation by receptors, and may be a general mechanism for prolonging or potentiating G-protein signaling.
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Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9041, USA.
Wang
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Ross
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EM
D000818:Animals; D002460:Cell Line; D004229:Dithiothreitol / Q000494:pharmacology; D044385:GTP-Binding Protein alpha Subunits; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins; D006868:Hydrolysis; D007700:Kinetics; D019308:Palmitic Acid / Q000378:metabolism*; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020710:RGS Proteins; D015398:Signal Transduction
C099387:GNAZ protein, human; D044385:GTP-Binding Protein alpha Subunits; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D011506:Proteins; D020710:RGS Proteins; C101113:RGS10 protein, human; C097187:regulator of G-protein signalling 19; C098799:RGS4 protein; D010171:Palmitoyl Coenzyme A; D019308:Palmitic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins; D004229:Dithiothreitol