Characterization of Glucagon-Like Peptide-1 Receptor β-Arrestin 2 Interaction: A High-Affinity Receptor Phenotype
To dissect the interaction between β-arrestin (βarr) and family B G protein-coupled receptors, we constructed fusion proteins between the glucagon-like peptide 1 receptor and βarr2. The fusion constructs had an increase in apparent affinity selectively for glucagon, suggesting that βarr2 interaction...
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Published in | Molecular endocrinology (Baltimore, Md.) Vol. 19; no. 3; pp. 812 - 823 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Endocrine Society
01.03.2005
Oxford University Press |
Subjects | |
Online Access | Get full text |
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Summary: | To dissect the interaction between β-arrestin (βarr) and family B G protein-coupled receptors, we constructed fusion proteins between the glucagon-like peptide 1 receptor and βarr2. The fusion constructs had an increase in apparent affinity selectively for glucagon, suggesting that βarr2 interaction locks the receptor in a high-affinity conformation, which can be explored by some, but not all, ligands. The fusion constructs adopted a signaling phenotype governed by the tethered βarr2 with an attenuated G protein-mediated cAMP signal and a higher maximal internalization compared with wild-type receptors. This distinct phenotype of the fusion proteins can not be mimicked by coexpressing wild-type receptor with βarr2. However, when the wild-type receptor was coexpressed with both βarr2 and G protein-coupled receptor kinase 5, a phenotype similar to that observed for the fusion constructs was observed. We conclude that the glucagon-like peptide 1 fusion construct mimics the natural interaction of the receptor with βarr2 with respect to binding peptide ligands, G protein-mediated signaling and internalization, and that this distinct molecular phenotype is reminiscent of that which has previously been characterized for family A G protein-coupled receptors, suggesting similarities in the effect of βarr interaction between family A and B receptors also at the molecular level. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0888-8809 1944-9917 |
DOI: | 10.1210/me.2004-0312 |