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

Nature. 1988 May 26;333(6171):370-3. doi: 10.1038/333370a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Cell Membrane / metabolism
  • Humans
  • Isoproterenol / pharmacology
  • Kinetics
  • Molecular Sequence Data
  • Molecular Weight
  • Mutation
  • Phosphorylation
  • Protein Conformation
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / genetics*
  • Receptors, Adrenergic, beta / physiology


  • Receptors, Adrenergic, beta
  • Isoproterenol