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

Jincheng Wang, Yan Xie, Dennis W. Wolff, Peter W. Abel, Yaping Tu

Research output: Contribution to journalArticle

18 Scopus citations


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 α1A-adrenergic receptor-stimulated intracellular Ca2+ mobilization. Together, our findings revealed that DHHC proteins could regulate GPCR-mediated signaling by increasing RGS4 stability. Structured summary: MINT- 8049215: Rgs4 (uniprotkb: P49799) physically interacts (MI: 0915) with DHHC3 (uniprotkb: Q8R173) by anti-tag coimmunoprecipitation (MI: 0007).

Original languageEnglish (US)
Pages (from-to)4570-4574
Number of pages5
JournalFEBS Letters
Issue number22
StatePublished - Nov 19 2010


All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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