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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).

Publication ,  Journal Article
Benovic, JL; Kühn, H; Weyand, I; Codina, J; Caron, MG; Lefkowitz, RJ
Published in: Proc Natl Acad Sci U S A
December 1987

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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

December 1987

Volume

84

Issue

24

Start / End Page

8879 / 8882

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Retina
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Phosphorylation
  • Phosphoproteins
  • In Vitro Techniques
  • Humans
  • GTP-Binding Proteins
  • Eye Proteins
 

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Benovic, J. L., Kühn, H., Weyand, I., Codina, J., Caron, M. G., & Lefkowitz, R. J. (1987). 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, 84(24), 8879–8882. https://doi.org/10.1073/pnas.84.24.8879
Benovic, J. L., H. Kühn, I. Weyand, J. Codina, M. G. Caron, and R. J. Lefkowitz. “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 84, no. 24 (December 1987): 8879–82. https://doi.org/10.1073/pnas.84.24.8879.
Benovic, J. L., et al. “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, vol. 84, no. 24, Dec. 1987, pp. 8879–82. Pubmed, doi:10.1073/pnas.84.24.8879.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

December 1987

Volume

84

Issue

24

Start / End Page

8879 / 8882

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Retina
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Phosphorylation
  • Phosphoproteins
  • In Vitro Techniques
  • Humans
  • GTP-Binding Proteins
  • Eye Proteins