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DHHC protein-dependent palmitoylation protects regulator of G-protein signaling 4 from proteasome degradation.

ABSTRACT: Regulator of G-protein signaling 4 (RGS4), an intracellular modulator of G-protein coupled receptor (GPCR)-mediated signaling, is regulated by multiple processes including palmitoylation and proteasome degradation. We found that co-expression of DHHC acyltransferases (DHHC3 or DHHC7), but not their acyltransferase-inactive mutants, increased expression levels of RGS4 but not its Cys2 to Ser mutant (RGS4C2S). DHHC3 interacts with and palmitoylates RGS4 but not RGS4C2S in vivo. Palmitoylation prolongs the half-life of RGS4 by over 8-fold and palmitoylated RGS4 blocked ?(1A)-adrenergic receptor-stimulated intracellular Ca(2+) mobilization. Together, our findings revealed that DHHC proteins could regulate GPCR-mediated signaling by increasing RGS4 stability.

SUBMITTER: Wang J

PROVIDER: S-EPMC2995692 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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DHHC protein-dependent palmitoylation protects regulator of G-protein signaling 4 from proteasome degradation.

Wang Jincheng J Xie Yan Y Wolff Dennis W DW Abel Peter W PW Tu Yaping Y

FEBS letters 20101028 22

Regulator of G-protein signaling 4 (RGS4), an intracellular modulator of G-protein coupled receptor (GPCR)-mediated signaling, is regulated by multiple processes including palmitoylation and proteasome degradation. We found that co-expression of DHHC acyltransferases (DHHC3 or DHHC7), but not their acyltransferase-inactive mutants, increased expression levels of RGS4 but not its Cys2 to Ser mutant (RGS4C2S). DHHC3 interacts with and palmitoylates RGS4 but not RGS4C2S in vivo. Palmitoylation prol ...[more]

PMID: 21035448

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