Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein)

Proc Natl Acad Sci U S A. 1987 Dec;84(24):8879-82. doi: 10.1073/pnas.84.24.8879.


The beta-adrenergic receptor kinase is an enzyme, possibly analogous to rhodopsin kinase, that multiply phosphorylates the beta-adrenergic receptor only when it is occupied by stimulatory agonists. Since this kinase may play an important role in mediating the process of homologous, or agonist-specific, desensitization, we investigated the functional consequences of receptor phosphorylation by the kinase and possible analogies with the mechanism of action of rhodopsin kinase. Pure hamster lung beta 2-adrenergic receptor, reconstituted in phospholipid vesicles, was assessed for its ability to mediate agonist-promoted stimulation of the GTPase activity of coreconstituted stimulatory guanine nucleotide-binding regulatory protein. When the receptor was phosphorylated by partially (approximately 350-fold) purified preparations of beta-adrenergic receptor kinase, as much as 80% inactivation of its functional activity was observed. However, the use of more highly purified enzyme preparations led to a dramatic decrease in the ability of phosphorylation to inactivate the receptor such that pure enzyme preparations (approximately 20,000-fold purified) caused only minimal (approximately 1off/- 7%) inactivation. Addition of pure retinal arrestin (48-kDa protein or S antigen), which is involved in enhancing the inactivating effect of rhodopsin phosphorylation by rhodopsin kinase, led to partial restoration of the functional effect of beta-adrenergic receptor kinase-promoted phosphorylation (41 +/- 3% inactivation). These results suggest the possibility that a protein analogous to retinal arrestin may exist in other tissues and function in concert with beta-adrenergic receptor kinase to regulate the activity of adenylate cyclase-coupled receptors.

MeSH terms

  • Animals
  • Antigens / metabolism*
  • Arrestin
  • Cyclic AMP-Dependent Protein Kinases*
  • Eye Proteins / metabolism*
  • GTP-Binding Proteins / metabolism*
  • Humans
  • In Vitro Techniques
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Receptors, Adrenergic, beta / metabolism*
  • Retina / physiology
  • beta-Adrenergic Receptor Kinases


  • Antigens
  • Arrestin
  • Eye Proteins
  • Phosphoproteins
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • beta-Adrenergic Receptor Kinases
  • GTP-Binding Proteins