HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Vázquez, P. Articles by Alvarez, E. Search for Related Content PubMed PubMed Citation Articles by Vázquez, P. Articles by Alvarez, E.

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain

(Requests for offprints should be addressed to Elvira Alvarez; Email: eao513{at}med.ucm.es)

In order to gain better insight into the molecular events involved in the signal transduction generated through glucagon-like peptide-1 (GLP-1) receptors, we tested the effect of deletions and point mutations within the cytoplasmic tail of this receptor with a view to establishing relationships between signal transduction desensitisation and receptor internalisation. Wild-type and truncated (deletion of the last 27 amino acids (GLPR 435R) and deletion of 44 amino acids (GLPR 418R)) GLP-1 receptors bound the agonist with similar affinity. Deletion of the last 27 amino acids decreased the internalisation rate by 78%, while deletion of 44 amino acids containing all the phosphorylation sites hitherto described in this receptor decreased the internalisation rate by only 47%. Binding of the ligand to both receptors stimulated adenylyl cyclase. In contrast, deletion of the region containing amino acids 419 to 435 (GLPR 419435) increased the internalisation rate by 268%, and the replacement of EVQ^408–410 by alanine (GLPR A^408–410) increased this process to 296%. In both receptors, the efficacy in stimulating adenylate cyclase was decreased. All the receptors studied were internalised by coated pits, except for the receptor with a deletion of the last 44 amino acids, which also had a faster resensitisation rate. Our findings indicate that the neighbouring trans-membrane domain of the carboxyl-terminal tail of the GLP-1 receptor contains sequence elements that regulate agonist-dependent internalisation and transmembrane signalling.

This article has been cited by other articles:

				W. Kim and J. M. Egan The Role of Incretins in Glucose Homeostasis and Diabetes Treatment Pharmacol. Rev., December 1, 2008; 60(4): 470 - 512. [Abstract] [Full Text] [PDF]

				K. G. Kumar, L. O. Byerley, J. Volaufova, D. J. Drucker, G. A. Churchill, R. Li, B. York, A. Zuberi, and B. K. S. Richards Genetic variation in Glp1r expression influences the rate of gastric emptying in mice Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R362 - R371. [Abstract] [Full Text] [PDF]