Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor.

Published

Journal Article

We report that a cysteine residue in the human beta 2-adrenergic receptor (beta 2AR) is covalently modified by thioesterification with palmitic acid. By site-directed mutagenesis of the receptor, we have identified Cys341 in the carboxyl tail of the protein as the most likely site of palmitoylation. Mutation of Cys341 to glycine results in a nonpalmitoylated form of the receptor that exhibits a drastically reduced ability to mediate isoproterenol stimulation of adenylyl cyclase. The functional impairment of this mutated beta 2AR is also reflected in a markedly reduced ability to form a guanyl nucleotide-sensitive high affinity state for agonists, characteristic of wild-type receptor. These results indicate that post-translational modification by palmitate of beta 2AR may play a crucial role in the normal coupling of the receptor to the adenylyl cyclase signal transduction system.

Full Text

Duke Authors

Cited Authors

  • O'Dowd, BF; Hnatowich, M; Caron, MG; Lefkowitz, RJ; Bouvier, M

Published Date

  • May 5, 1989

Published In

Volume / Issue

  • 264 / 13

Start / End Page

  • 7564 - 7569

PubMed ID

  • 2540197

Pubmed Central ID

  • 2540197

International Standard Serial Number (ISSN)

  • 0021-9258

Language

  • eng

Conference Location

  • United States