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 language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Mar 29 1994|
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