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Beta-adrenergic receptor-coupled adenylate cyclase. Biochemical mechanisms of regulation.

Publication ,  Journal Article
Sibley, DR; Lefkowitz, RJ
Published in: Mol Neurobiol
1987

Beta-adrenergic receptor-coupled adenylate cyclase is regulated by both amplification and desensitization processes. Desensitization of adenylate cyclase is divided into two major categories. Homologous desensitization is initiated by phosphorylation of the receptors by a beta-adrenergic receptor kinase. This reaction serves to functionally uncouple the receptors and trigger their sequestration away from the cell surface. These sequestered receptors can rapidly recycle to the cell surface or, with time, become down regulated, being destroyed within the cell. Dephosphorylation of the receptors is accomplished in the sequestered compartment of the cell, which may functionally regenerate the receptors and allow their return to the cell surface. In heterologous desensitization, receptor function is also regulated by phosphorylation, but in the absence of receptor sequestration or down regulation. In this case, phosphorylation serves only to functionally uncouple the receptors, that is, to impair their interactions with the guanine nucleotide regulatory protein Ns. Several protein kinases are capable of promoting this phosphorylation, including the cAMP-dependent kinase and protein kinase C. In addition to the receptor phosphorylation, heterologous desensitization is associated with modifications at the level of the nucleotide regulatory protein Ns and perhaps Ni. Adenylate cyclase systems are also subject to amplification that involves a protein kinase C-mediated phosphorylation of the catalytic unit of the enzyme. Phosphorylation of the catalytic unit enhances its catalytic activity and results in amplified stimulation by the regulatory protein Ns. Other receptor/effector systems exhibit qualitatively similar regulatory phenomena, suggesting that covalent modification (phosphorylation) may represent a general mechanism for regulating receptor function.

Duke Scholars

Published In

Mol Neurobiol

DOI

ISSN

0893-7648

Publication Date

1987

Volume

1

Issue

1-2

Start / End Page

121 / 154

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Phosphorylation
  • Neurons
  • Neurology & Neurosurgery
  • Animals
  • Adenylyl Cyclases
  • 3209 Neurosciences
  • 3101 Biochemistry and cell biology
  • 1702 Cognitive Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sibley, D. R., & Lefkowitz, R. J. (1987). Beta-adrenergic receptor-coupled adenylate cyclase. Biochemical mechanisms of regulation. Mol Neurobiol, 1(1–2), 121–154. https://doi.org/10.1007/BF02935266
Sibley, D. R., and R. J. Lefkowitz. “Beta-adrenergic receptor-coupled adenylate cyclase. Biochemical mechanisms of regulation.Mol Neurobiol 1, no. 1–2 (1987): 121–54. https://doi.org/10.1007/BF02935266.
Sibley DR, Lefkowitz RJ. Beta-adrenergic receptor-coupled adenylate cyclase. Biochemical mechanisms of regulation. Mol Neurobiol. 1987;1(1–2):121–54.
Sibley, D. R., and R. J. Lefkowitz. “Beta-adrenergic receptor-coupled adenylate cyclase. Biochemical mechanisms of regulation.Mol Neurobiol, vol. 1, no. 1–2, 1987, pp. 121–54. Pubmed, doi:10.1007/BF02935266.
Sibley DR, Lefkowitz RJ. Beta-adrenergic receptor-coupled adenylate cyclase. Biochemical mechanisms of regulation. Mol Neurobiol. 1987;1(1–2):121–154.
Journal cover image

Published In

Mol Neurobiol

DOI

ISSN

0893-7648

Publication Date

1987

Volume

1

Issue

1-2

Start / End Page

121 / 154

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Phosphorylation
  • Neurons
  • Neurology & Neurosurgery
  • Animals
  • Adenylyl Cyclases
  • 3209 Neurosciences
  • 3101 Biochemistry and cell biology
  • 1702 Cognitive Sciences