Myristoylated alpha subunits of guanine nucleotide-binding regulatory proteins.
Antisera directed against specific subunits of guanine nucleotide-binding regulatory proteins (G proteins) were used to immunoprecipitate these polypeptides from metabolically labeled cells. This technique detects, in extracts of a human astrocytoma cell line, the alpha subunits of Gs (stimulatory) (alpha 45 and alpha 52), a 41-kDa subunit of Gi (inhibitory) (alpha 41), a 40-kDa protein (alpha 40), and the 36-kDa beta subunit. No protein that comigrated with the alpha subunit of Go (unknown function) (alpha 39) was detected. In cells grown in the presence of [3H]myristic acid, alpha 41 and alpha 40 contained 3H label, while the beta subunit did not. Chemical analysis of lipids attached covalently to purified alpha 41 and alpha 39 from bovine brain also revealed myristic acid. Similar analysis of brain G protein beta and gamma subunits and of Gt (transducin) subunits (alpha, beta, and gamma) failed to reveal fatty acids. The fatty acid associated with alpha 41, alpha 40, and alpha 39 was stable to treatment with base, suggesting that the lipid is linked to the polypeptide via an amide bond. These GTP binding proteins are thus identified as members of a select group of proteins that contains myristic acid covalently attached to the peptide backbone. Myristate may play an important role in stabilizing interactions of G proteins with phospholipid or with membrane-bound proteins.
D000818:Animals; D001254:Astrocytoma; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000302:isolation & purification*; D006801:Humans; D046911:Macromolecular Substances; D008970:Molecular Weight; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism; D014316:Tritium
D046911:Macromolecular Substances; D009227:Myristic Acids; D019814:Myristic Acid; D014316:Tritium; D019204:GTP-Binding Proteins