Receptor regulation of G-protein palmitoylation

Susanne M. Mumby, Christiane Kleuss, Alfred G. Gilman

Research output: Contribution to journalArticle

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Abstract

Many α subunits of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) are palmitoylated. Exposure of cells to the β- adrenergic agonist isoproterenol increased incorporation of [3H]palmitate specifically into α(s), the α subunit that mediates stimulation of adenylyl cyclase. Pulse-chase experiments suggested that isoproterenol increased turnover of α(s)-bound palmitate. Mutagenesis of Cys-3 in α(s) or α(o) (a homologous α subunit) prevented palmitoylation of these proteins. Differing results were obtained when mutations of Cys-3 in α(s) or α(o) were expressed in cells and assayed for their distribution between soluble and membrane fractions. Some α subunits, including α(o), are myristoylated at the amino-terminal glycine residue. Mutation of this glycine prevented both myristoylation and palmitoylation of α(o), indicating that myristoylation precedes palmitoylation of dually acylated α subunits. The amino-terminal sequences and fatty acylation properties of dually acylated α subunits are strikingly similar to those of some members of the Src family of protein- tyrosine kinases. The amino-terminal sequence Met-Gly-Cys-Xaa-Xaa-Ser/Cys shared by these proteins may represent a motif for cotranslational and posttranslational processing that includes myristoylation of the glycine residue and reversible palmitoylation of the cysteine residue.

Original languageEnglish (US)
Pages (from-to)2800-2804
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number7
StatePublished - Mar 29 1994

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Lipoylation
GTP-Binding Proteins
Glycine
src-Family Kinases
Palmitates
Isoproterenol
Adrenergic Agonists
Mutation
Acylation
Adenylyl Cyclases
Mutagenesis
Cysteine
Carrier Proteins
Proteins
Membranes

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Receptor regulation of G-protein palmitoylation. / Mumby, Susanne M.; Kleuss, Christiane; Gilman, Alfred G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 7, 29.03.1994, p. 2800-2804.

Research output: Contribution to journalArticle

Mumby, Susanne M. ; Kleuss, Christiane ; Gilman, Alfred G. / Receptor regulation of G-protein palmitoylation. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 7. pp. 2800-2804.
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