Skip to main content

Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation.

Publication ,  Journal Article
Kjelsberg, MA; Cotecchia, S; Ostrowski, J; Caron, MG; Lefkowitz, RJ
Published in: J Biol Chem
January 25, 1992

Mutations in an intracellular region of the alpha 1B-adrenergic receptor constitutively activate the receptor, resulting in G protein coupling in the absence of agonist, as evidenced by elevated levels of polyphosphoinositide hydrolysis. Remarkably, all 19 possible amino acid substitutions at a single site in this region (alanine 293) confer constitutive activity. This set of mutated receptors exhibits a graded range of elevated biological activities, apparently representing a spectrum of receptor conformations which mimic the "active" state of the wild type receptor. In addition to their constitutive activities, these mutated receptors all demonstrate a higher affinity for agonists, another primary characteristic of the "active" conformation of G protein-coupled receptors. The fact that all possible mutations at this particular site result in increased activity suggests that this region may function to constrain the G protein coupling of the receptor, a constraint which is normally relieved by agonist occupancy.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

January 25, 1992

Volume

267

Issue

3

Start / End Page

1430 / 1433

Location

United States

Related Subject Headings

  • Transfection
  • Tetralones
  • Receptors, Adrenergic, beta
  • Protein Conformation
  • Phenethylamines
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Models, Structural
  • Kinetics
  • Inositol Phosphates
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kjelsberg, M. A., Cotecchia, S., Ostrowski, J., Caron, M. G., & Lefkowitz, R. J. (1992). Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation. J Biol Chem, 267(3), 1430–1433.
Kjelsberg, M. A., S. Cotecchia, J. Ostrowski, M. G. Caron, and R. J. Lefkowitz. “Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation.J Biol Chem 267, no. 3 (January 25, 1992): 1430–33.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

January 25, 1992

Volume

267

Issue

3

Start / End Page

1430 / 1433

Location

United States

Related Subject Headings

  • Transfection
  • Tetralones
  • Receptors, Adrenergic, beta
  • Protein Conformation
  • Phenethylamines
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Models, Structural
  • Kinetics
  • Inositol Phosphates