Regions of the alpha 1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function.

Détails

ID Serval
serval:BIB_340DDFB780DA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Regions of the alpha 1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Cotecchia S., Exum S., Caron M.G., Lefkowitz R.J.
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
1990
Volume
87
Numéro
8
Pages
2896-2900
Langue
anglais
Résumé
Regions of the hamster alpha 1-adrenergic receptor (alpha 1 AR) that are important in GTP-binding protein (G protein)-mediated activation of phospholipase C were determined by studying the biological functions of mutant receptors constructed by recombinant DNA techniques. A chimeric receptor consisting of the beta 2-adrenergic receptor (beta 2AR) into which the putative third cytoplasmic loop of the alpha 1AR had been placed activated phosphatidylinositol metabolism as effectively as the native alpha 1AR, as did a truncated alpha 1AR lacking the last 47 residues in its cytoplasmic tail. Substitutions of beta 2AR amino acid sequence in the intermediate portions of the third cytoplasmic loop of the alpha 1AR or at the N-terminal portion of the cytoplasmic tail caused marked decreases in receptor coupling to phospholipase C. Conservative substitutions of two residues in the C terminus of the third cytoplasmic loop (Ala293----Leu, Lys290----His) increased the potency of agonists for stimulating phosphatidylinositol metabolism by up to 2 orders of magnitude. These data indicate (i) that the regions of the alpha 1AR that determine coupling to phosphatidylinositol metabolism are similar to those previously shown to be involved in coupling of beta 2AR to adenylate cyclase stimulation and (ii) that point mutations of a G-protein-coupled receptor can cause remarkable increases in sensitivity of biological response.
Mots-clé
Amino Acid Sequence, Animals, Cell Line, Cricetinae, Hydrolysis, Inositol/metabolism, Inositol Phosphates/metabolism, Kinetics, Ligands, Molecular Sequence Data, Norepinephrine/metabolism, Norepinephrine/pharmacology, Phosphatidylinositols/metabolism, Plasmids, Protein Conformation, Receptors, Adrenergic, alpha/drug effects, Receptors, Adrenergic, alpha/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 12:05
Dernière modification de la notice
08/05/2019 16:52
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