Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization.

Published

Journal Article

Eukaryotic cells have evolved a variety of mechanisms for dampening their responsiveness to hormonal stimulation in the face of sustained activation. The mechanisms for such processes, collectively referred to as desensitization, often involve alterations in the properties and number of cell-surface hormone receptors. It has been speculated that phosphorylation-dephosphorylation reactions, which are known to regulate the catalytic activities of enzymes, also regulate the function of receptors. Highly specific receptor kinases, such as rhodopsin kinase and beta-adrenergic receptor kinase, which show stimulus-dependent phosphorylation of receptors have been described. Direct evidence for a causal relationship between receptor phosphorylation and desensitization has been lacking however. Here we report that prevention of agonist-stimulated beta 2-adrenergic receptor (beta 2AR) phosphorylation by truncation of its serine and threonine-rich phosphate acceptor segment delays the onset of desensitization. We also show that selective replacement of these serine and threonine residues by alanine and glycine delays desensitization even further. These data provide the first direct evidence that one molecular mechanism of desensitization of G-protein-coupled receptors involves their agonist-induced phosphorylation.

Full Text

Duke Authors

Cited Authors

  • Bouvier, M; Hausdorff, WP; De Blasi, A; O'Dowd, BF; Kobilka, BK; Caron, MG; Lefkowitz, RJ

Published Date

  • May 26, 1988

Published In

Volume / Issue

  • 333 / 6171

Start / End Page

  • 370 - 373

PubMed ID

  • 2836733

Pubmed Central ID

  • 2836733

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/333370a0

Language

  • eng

Conference Location

  • England