Inhibition of brain G(z) GAP and other RGS proteins by palmitoylation of G protein α subunits

Yaping Tu, Jun Wang, Elliott M. Ross

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Palmitoylation of the α subunit of the guanine nucleotide-binding protein G(z) inhibited by more than 90 percent its response to the guanosine triphosphatase (GTPase)-accelerating activity of G(z) GAP, a G(z)-selective member of the regulators of G-protein signaling (RGS) protein family of GTPase-activating proteins (GAPs). Palmitoylation both decreased the affinity of G(z) GAP for the GTP-bound form of Gα(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 Gα(z) also inhibited its response to the GAP activity of Gα-interacting Protein (GAIP), another RGS protein, and palmitoylation of Gα(l1) inhibited its response to RGS4. The extent of inhibition of G(z) GAP, GAIP, RGS4, and RGS10 correlated roughly with their intrinsic GAP activities for the Gα target used in the assay. Reversible palmitoylation is thus a major determinant of G(z) deactivation after its stimulation by receptors, and may be a general mechanism for prolonging or potentiating G-protein signaling.

Original languageEnglish
Pages (from-to)1132-1135
Number of pages4
JournalScience
Volume278
Issue number5340
DOIs
StatePublished - Nov 7 1997
Externally publishedYes

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RGS Proteins
Lipoylation
GTPase-Activating Proteins
Protein Subunits
GTP-Binding Proteins
Brain
Guanosine
Guanosine Triphosphate
Guanine Nucleotides
Dithiothreitol
Carrier Proteins
Proteins
Hydrolysis

All Science Journal Classification (ASJC) codes

  • General

Cite this

Inhibition of brain G(z) GAP and other RGS proteins by palmitoylation of G protein α subunits. / Tu, Yaping; Wang, Jun; Ross, Elliott M.

In: Science, Vol. 278, No. 5340, 07.11.1997, p. 1132-1135.

Research output: Contribution to journalArticle

Tu, Yaping ; Wang, Jun ; Ross, Elliott M. / Inhibition of brain G(z) GAP and other RGS proteins by palmitoylation of G protein α subunits. In: Science. 1997 ; Vol. 278, No. 5340. pp. 1132-1135.
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AB - Palmitoylation of the α subunit of the guanine nucleotide-binding protein G(z) inhibited by more than 90 percent its response to the guanosine triphosphatase (GTPase)-accelerating activity of G(z) GAP, a G(z)-selective member of the regulators of G-protein signaling (RGS) protein family of GTPase-activating proteins (GAPs). Palmitoylation both decreased the affinity of G(z) GAP for the GTP-bound form of Gα(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 Gα(z) also inhibited its response to the GAP activity of Gα-interacting Protein (GAIP), another RGS protein, and palmitoylation of Gα(l1) inhibited its response to RGS4. The extent of inhibition of G(z) GAP, GAIP, RGS4, and RGS10 correlated roughly with their intrinsic GAP activities for the Gα target used in the assay. Reversible palmitoylation is thus a major determinant of G(z) deactivation after its stimulation by receptors, and may be a general mechanism for prolonging or potentiating G-protein signaling.

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