Truncation of the receptor carboxyl terminus impairs agonist-dependent phosphorylation and desensitization of the alpha 1B-adrenergic receptor.

Détails

ID Serval
serval:BIB_1E5171918500
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Truncation of the receptor carboxyl terminus impairs agonist-dependent phosphorylation and desensitization of the alpha 1B-adrenergic receptor.
Périodique
Journal of Biological Chemistry
Auteur(s)
Lattion A.L., Diviani D., Cotecchia S.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
1994
Volume
269
Numéro
36
Pages
22887-22893
Langue
anglais
Résumé
The alpha 1B-adrenergic receptor (alpha 1BAR) and its truncated mutant T368 lacking the last 147 amino acids were stably expressed in Rat1 fibroblasts. The wild type alpha 1BAR was rapidly phosphorylated upon exposure to the agonist epinephrine as well as to phorbol ester as assessed by immunoprecipitation of the receptor with antiserum raised against its amino-terminal portion. Exposure of cells expressing the wild type alpha 1BAR to epinephrine resulted also in rapid homologous desensitization of receptor-mediated response on polyphosphoinositide hydrolysis. On the other hand, truncation of the serine- and threonine-rich carboxyl portion of the alpha 1BAR abolished agonist-induced phosphorylation and greatly impaired homologous desensitization of the receptor. The truncated receptor T368 could undergo agonist-induced decrease of cell surface receptors but to a lesser extent, as compared with the wild type alpha 1BAR. These results demonstrate that the carboxyl portion of the alpha 1BAR plays a crucial role in the regulation of receptor function. They also suggest a strong relationship between agonist-induced phosphorylation and desensitization of the alpha 1BAR, which were both insensitive to the inhibitor of protein kinase C RO-318220. Our findings support the emerging hypothesis that the biochemical mechanisms involved in rapid agonist-dependent regulation of G protein-coupled receptors, which activate polyphosphoinositide hydrolysis, do not primarily involve protein kinase C.
Mots-clé
Animals, Cell Line, Cell Membrane/metabolism, Cercopithecus aethiops, Epinephrine/pharmacology, Fibroblasts/drug effects, Fibroblasts/metabolism, Indoles/pharmacology, Inositol 1,4,5-Trisphosphate/metabolism, Kinetics, Phosphatidylinositol Phosphates/metabolism, Phosphorylation, Protein Kinase C/antagonists & inhibitors, Rats, Receptors, Adrenergic, alpha-1/biosynthesis, Receptors, Adrenergic, alpha-1/drug effects, Recombinant Proteins/biosynthesis, Recombinant Proteins/drug effects, Sequence Deletion, Serine, Threonine, Transfection
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 12:54
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