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Agonist-promoted coupling of the beta-adrenergic receptor with the guanine nucleotide regulatory protein of the adenylate cyclase system.

Publication ,  Journal Article
Limbird, LE; Gill, DM; Lefkowitz, RJ
Published in: Proc Natl Acad Sci U S A
February 1980

Binding of the beta-adrenergic agonist [3H]hydroxybenzylisoproterenol to the beta-adrenergic receptor of rat reticulocyte membranes results in the coupling of the receptor to the guanine nucleotide regulatory protein associated with the adenylate cyclase system. This regulatory component, referred to as the G-protein, was identified by its specific [32P]-ADP-ribosylation catalyzed by cholera toxin. Incubation of [32P]ADP-ribosylated rat reticulocyte membranes with the [3H]hydroxybenzylisoproterenol agonist prior to membrane solubilization and gel exclusion chromatography resulted in the coelution of the 42,000 Mr [32P]ADP-ribosylated G-proteins with the agonist-occupied beta-adrenergic receptors. The receptor-G-protein complex was not formed when receptors were unoccupied or occupied with antagonists at the time of solubilization. Incubation of rat reticulocyte membranes with [3H]hydroxybenzylisoproterenol in the presence of guanine nucleotides reversed or prevented the formation of this receptor-G-protein complex. These data provide direct evidence for the molecular interactions promoted by agonist occupancy of beta-adrenergic receptors. It is probable that the formation of a receptor-G-protein complex is crucial for catecholamine stimulation of the adenylate cyclase enzyme and, hence, transmembrane information transfer.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 1980

Volume

77

Issue

2

Start / End Page

775 / 779

Location

United States

Related Subject Headings

  • Reticulocytes
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic
  • Rats
  • NAD
  • Molecular Weight
  • Membrane Proteins
  • Guanosine Triphosphate
  • Enzyme Activation
  • Cholera Toxin
 

Citation

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Limbird, L. E., Gill, D. M., & Lefkowitz, R. J. (1980). Agonist-promoted coupling of the beta-adrenergic receptor with the guanine nucleotide regulatory protein of the adenylate cyclase system. Proc Natl Acad Sci U S A, 77(2), 775–779. https://doi.org/10.1073/pnas.77.2.775
Limbird, L. E., D. M. Gill, and R. J. Lefkowitz. “Agonist-promoted coupling of the beta-adrenergic receptor with the guanine nucleotide regulatory protein of the adenylate cyclase system.Proc Natl Acad Sci U S A 77, no. 2 (February 1980): 775–79. https://doi.org/10.1073/pnas.77.2.775.
Limbird, L. E., et al. “Agonist-promoted coupling of the beta-adrenergic receptor with the guanine nucleotide regulatory protein of the adenylate cyclase system.Proc Natl Acad Sci U S A, vol. 77, no. 2, Feb. 1980, pp. 775–79. Pubmed, doi:10.1073/pnas.77.2.775.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 1980

Volume

77

Issue

2

Start / End Page

775 / 779

Location

United States

Related Subject Headings

  • Reticulocytes
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic
  • Rats
  • NAD
  • Molecular Weight
  • Membrane Proteins
  • Guanosine Triphosphate
  • Enzyme Activation
  • Cholera Toxin