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Research ArticleArticle

Palmitoylation and Plasma Membrane Targeting of RGS7 Are Promoted by αo

Satoshi Takida, Christopher C. Fischer and Philip B. Wedegaertner
Molecular Pharmacology January 2005, 67 (1) 132-139; DOI: https://doi.org/10.1124/mol.104.003418
Satoshi Takida
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Christopher C. Fischer
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Philip B. Wedegaertner
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Abstract

Regulator of G protein signaling (RGS) proteins modulate G protein signaling by acting as GTPase-activating proteins for G protein α-subunits. RGS7 belongs to a subfamily of RGS proteins that exist as dimers with the G protein β5-subunit. In this report, we addressed the mechanisms of plasma membrane localization of β5RGS7. When expressed in human embryonic kidney 293 cells, β5RGS7 was found to be cytoplasmic and soluble. Expression of αo promoted a strong redistribution of β5RGS7 to the plasma membrane. Expression of αq, however, failed to affect the subcellular localization of β5RGS7. The constitutively active mutant αoR179C, like wild-type αo, strongly recruited β5RGS7 to plasma membranes; however, inactive αoG204A, RGS-insensitive αoG184S, and lipidation-deficient αoG2A were all defective in the ability to promote plasma membrane localization of β5RGS7. In addition, palmitoylation of RGS7 was demonstrated, and palmitoylation required expression of αo or αoR179C. To examine potential palmitoylation sites of RGS7, several cysteines were substituted with serines. β5RGS7C133S failed to localize to plasma membranes when coexpressed with αo, suggesting cysteine 133 of RGS7 as a putative palmitoylation site. Finally, deletion of amino acids 76 to 128 of RGS7, which includes part of the disheveled, EGL-10, pleckstrin (DEP) domain, prevented αo-mediated plasma membrane recruitment of β5RGS7. These findings are the first to demonstrate Gα-regulated plasma membrane localization and palmitoylation of β5RGS7 and suggest that membrane targeting of β5RGS7 is a complex process requiring at least RGS domain-mediated interaction with αo and RGS7 palmitoylation.

  • Received June 1, 2004.
  • Accepted October 19, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 67 (1)
Molecular Pharmacology
Vol. 67, Issue 1
1 Jan 2005
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Research ArticleArticle

Palmitoylation and Plasma Membrane Targeting of RGS7 Are Promoted by αo

Satoshi Takida, Christopher C. Fischer and Philip B. Wedegaertner
Molecular Pharmacology January 1, 2005, 67 (1) 132-139; DOI: https://doi.org/10.1124/mol.104.003418

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Research ArticleArticle

Palmitoylation and Plasma Membrane Targeting of RGS7 Are Promoted by αo

Satoshi Takida, Christopher C. Fischer and Philip B. Wedegaertner
Molecular Pharmacology January 1, 2005, 67 (1) 132-139; DOI: https://doi.org/10.1124/mol.104.003418
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