Skip to main content

Molecular mechanisms of beta-adrenergic receptor desensitization.

Publication ,  Journal Article
Sibley, DR; Benovic, JL; Caron, MG; Lefkowitz, RJ
Published in: Adv Exp Med Biol
1987

Multiple mechanisms seem to be involved in regulating the responsiveness of hormone receptor-coupled adenylate cyclase systems. These mechanisms at least involve the receptors and nucleotide regulatory proteins. With the recent development of methods for purifying the catalytic unit of the enzyme it will be possible to assess whether it is also a locus for such regulatory phenomena. At least two major pathways of receptor regulation have been uncovered. Homologous desensitization (Fig. 9) involves the uncoupling and translocation of the receptors out of their normal plasma membrane environment. This process sequesters the receptors away from their effector, the regulatory and catalytic components of adenylate cyclase. The site of receptor sequestration is unclear and might lie within the plasma membrane or within the cell. The sequestered receptors can recycle to the cell surface or become down-regulated, perhaps being destroyed within the cell. Phosphorylation of the receptors through a beta-adrenergic receptor kinase appears to be associated with homologous desensitization. This phosphorylation event may serve either to uncouple functionally the receptors or to trigger their sequestration from the cell surface or both. In heterologous desensitization (Fig. 10), receptor function is regulated by phosphorylation in the absence of receptor sequestration or down-regulation. This covalent modification serves to functionally uncouple the receptors, that is, to impair their interactions with the guanine nucleotide regulatory proteins. Several protein kinases seem to be capable of promoting phosphorylation of the receptors including the cAMP-dependent kinase and protein kinase C. In addition to the receptor modification, heterologous desensitization seems to be associated with functional modifications (phosphorylation?) at the level of nucleotide regulatory proteins (Ns and Ni), (Fig. 10). Further studies of the mechanisms of desensitization of adenylate cyclase-coupled receptors are thus likely to help elucidate modes of regulation of a wide variety of receptor-coupled functions in diverse types of cells.

Duke Scholars

Published In

Adv Exp Med Biol

DOI

ISSN

0065-2598

Publication Date

1987

Volume

221

Start / End Page

253 / 273

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Phosphorylation
  • Models, Biological
  • Homeostasis
  • General & Internal Medicine
  • Animals
  • Adenylyl Cyclases
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sibley, D. R., Benovic, J. L., Caron, M. G., & Lefkowitz, R. J. (1987). Molecular mechanisms of beta-adrenergic receptor desensitization. Adv Exp Med Biol, 221, 253–273. https://doi.org/10.1007/978-1-4684-7618-7_19
Sibley, D. R., J. L. Benovic, M. G. Caron, and R. J. Lefkowitz. “Molecular mechanisms of beta-adrenergic receptor desensitization.Adv Exp Med Biol 221 (1987): 253–73. https://doi.org/10.1007/978-1-4684-7618-7_19.
Sibley DR, Benovic JL, Caron MG, Lefkowitz RJ. Molecular mechanisms of beta-adrenergic receptor desensitization. Adv Exp Med Biol. 1987;221:253–73.
Sibley, D. R., et al. “Molecular mechanisms of beta-adrenergic receptor desensitization.Adv Exp Med Biol, vol. 221, 1987, pp. 253–73. Pubmed, doi:10.1007/978-1-4684-7618-7_19.
Sibley DR, Benovic JL, Caron MG, Lefkowitz RJ. Molecular mechanisms of beta-adrenergic receptor desensitization. Adv Exp Med Biol. 1987;221:253–273.

Published In

Adv Exp Med Biol

DOI

ISSN

0065-2598

Publication Date

1987

Volume

221

Start / End Page

253 / 273

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Phosphorylation
  • Models, Biological
  • Homeostasis
  • General & Internal Medicine
  • Animals
  • Adenylyl Cyclases
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences