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.

Détails

ID Serval
serval:BIB_5F6813D9CACA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
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.
Périodique
Journal of Biological Chemistry
Auteur(s)
Kjelsberg M.A., Cotecchia S., Ostrowski J., Caron M.G., Lefkowitz R.J.
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
1992
Peer-reviewed
Oui
Volume
267
Numéro
3
Pages
1430-1433
Langue
anglais
Résumé
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.
Mots-clé
Adrenergic beta-Agonists/metabolism, Amino Acid Sequence, Animals, Binding Sites, Binding, Competitive, Cell Line, Cell Membrane/metabolism, DNA/genetics, Epinephrine/metabolism, Epinephrine/pharmacology, Inositol Phosphates/metabolism, Kinetics, Models, Structural, Molecular Sequence Data, Mutagenesis, Site-Directed, Phenethylamines/metabolism, Protein Conformation, Receptors, Adrenergic, beta/genetics, Receptors, Adrenergic, beta/metabolism, Tetralones, Transfection
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 14:17
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