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

Details

Serval ID
serval:BIB_1E5171918500
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Truncation of the receptor carboxyl terminus impairs agonist-dependent phosphorylation and desensitization of the alpha 1B-adrenergic receptor.
Journal
Journal of Biological Chemistry
Author(s)
Lattion A.L., Diviani D., Cotecchia S.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Publication state
Published
Issued date
1994
Volume
269
Number
36
Pages
22887-22893
Language
english
Abstract
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.
Keywords
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
Create date
24/01/2008 11:05
Last modification date
20/08/2019 12:54
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