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The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression
GLP-1R (glucagon-like peptide-1 receptor) mediates the ‘incretin effect’ and many other anti-diabetic actions of its cognate ligand, GLP-1 (glucagon-like peptide-1). It belongs to the class B family of GPCRs (G protein-coupled receptors) and possesses an N-terminal putative SP (signal peptide). It h...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240022/ https://www.ncbi.nlm.nih.gov/pubmed/25330813 http://dx.doi.org/10.1042/BSR20140120 |
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author | Ge, Yunjun Yang, Dehua Dai, Antao Zhou, Caihong Zhu, Yue Wang, Ming-Wei |
author_facet | Ge, Yunjun Yang, Dehua Dai, Antao Zhou, Caihong Zhu, Yue Wang, Ming-Wei |
author_sort | Ge, Yunjun |
collection | PubMed |
description | GLP-1R (glucagon-like peptide-1 receptor) mediates the ‘incretin effect’ and many other anti-diabetic actions of its cognate ligand, GLP-1 (glucagon-like peptide-1). It belongs to the class B family of GPCRs (G protein-coupled receptors) and possesses an N-terminal putative SP (signal peptide). It has been reported that this sequence is required for the synthesis of GLP-1R and is cleaved after receptor synthesis. In the present study, we conducted an in-depth exploration towards the role of the putative SP in GLP-1R synthesis. A mutant GLP-1R without this sequence was expressed in HEK293 cells (human embryonic kidney 293 cells) and displayed normal functionality with respect to ligand binding and activation of adenylate cyclase. Thus the putative SP does not seem to be required for receptor synthesis. Immunoblotting analysis shows that the amount of GLP-1R synthesized in HEK293 cells is low when the putative SP is absent. This indicates that the role of the sequence is to promote the expression of GLP-1R. Furthermore, epitopes tagged at the N-terminal of GLP-1R are detectable by immunofluorescence and immunoblotting in our experiments. In conclusion, the present study points to different roles of SP in GLP-1R expression which broadens our understanding of the functionality of this putative SP of GLP-1R and possibly other Class B GPCRs. |
format | Online Article Text |
id | pubmed-4240022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-42400222014-12-01 The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression Ge, Yunjun Yang, Dehua Dai, Antao Zhou, Caihong Zhu, Yue Wang, Ming-Wei Biosci Rep Original Paper GLP-1R (glucagon-like peptide-1 receptor) mediates the ‘incretin effect’ and many other anti-diabetic actions of its cognate ligand, GLP-1 (glucagon-like peptide-1). It belongs to the class B family of GPCRs (G protein-coupled receptors) and possesses an N-terminal putative SP (signal peptide). It has been reported that this sequence is required for the synthesis of GLP-1R and is cleaved after receptor synthesis. In the present study, we conducted an in-depth exploration towards the role of the putative SP in GLP-1R synthesis. A mutant GLP-1R without this sequence was expressed in HEK293 cells (human embryonic kidney 293 cells) and displayed normal functionality with respect to ligand binding and activation of adenylate cyclase. Thus the putative SP does not seem to be required for receptor synthesis. Immunoblotting analysis shows that the amount of GLP-1R synthesized in HEK293 cells is low when the putative SP is absent. This indicates that the role of the sequence is to promote the expression of GLP-1R. Furthermore, epitopes tagged at the N-terminal of GLP-1R are detectable by immunofluorescence and immunoblotting in our experiments. In conclusion, the present study points to different roles of SP in GLP-1R expression which broadens our understanding of the functionality of this putative SP of GLP-1R and possibly other Class B GPCRs. Portland Press Ltd. 2014-11-21 /pmc/articles/PMC4240022/ /pubmed/25330813 http://dx.doi.org/10.1042/BSR20140120 Text en © 2014 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY) (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY) (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Paper Ge, Yunjun Yang, Dehua Dai, Antao Zhou, Caihong Zhu, Yue Wang, Ming-Wei The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression |
title | The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression |
title_full | The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression |
title_fullStr | The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression |
title_full_unstemmed | The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression |
title_short | The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression |
title_sort | putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240022/ https://www.ncbi.nlm.nih.gov/pubmed/25330813 http://dx.doi.org/10.1042/BSR20140120 |
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