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Science 7 November 1997:
Vol. 278. no. 5340, pp. 1132 - 1135
DOI: 10.1126/science.278.5340.1132
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Reports

Inhibition of Brain Gz GAP and Other RGS Proteins by Palmitoylation of G Protein alpha  Subunits

Yaping Tu, Jun Wang, Elliott M. Ross *

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 Galpha z 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 Galpha z also inhibited its response to the GAP activity of Galpha -interacting protein (GAIP), another RGS protein, and palmitoylation of Galpha i1 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.

Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9041, USA.
*   To whom correspondence should be addressed.

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