Tyr(1) and Ile(7) of Glucose-Dependent Insulinotropic Polypeptide (GIP) Confer Differential Ligand Selectivity toward GIP and Glucagon-like Peptide-1 Receptors
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Moon, Mi Jin | - |
dc.contributor.author | Kim, Hee Young | - |
dc.contributor.author | Kim, Sin Gon | - |
dc.contributor.author | Park, Juri | - |
dc.contributor.author | Choi, Dong Seop | - |
dc.contributor.author | Hwang, Jong-Ik | - |
dc.contributor.author | Seong, Jae Young | - |
dc.date.accessioned | 2021-09-08T01:22:56Z | - |
dc.date.available | 2021-09-08T01:22:56Z | - |
dc.date.created | 2021-06-14 | - |
dc.date.issued | 2010-08 | - |
dc.identifier.issn | 1016-8478 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/116013 | - |
dc.description.abstract | Glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones released in response to food intake and potentiate insulin secretion from pancreatic beta cells through their distinct yet related G protein-coupled receptors, GLP1R and GIPR. While GLP-1 and GIP exhibit similarity in their N-terminal sequence and overall alpha-helical structure, GLP-1 does not bind to GIPR and vice versa. To determine which amino acid residues of these peptide ligands are responsible for specific interaction with their respective receptors, we generated mutant GIP in which several GLP-1-specific amino acid residues were substituted for the original amino acids. The potency of the mutant ligands was examined using HEK293 cells transfected with GLP1R or GIPR expression plasmids together with a cAMP-responsive element-driven luciferase (CRE-luc) reporter plasmid. A mutated GIP peptide in which Tyr(1), Ile(7), Asp(15), and His(18) were replaced by His, Thr, Glu, and Ala, respectively, was able to activate both GLP1R and GIPR with moderate potency. Replacing the original Tyr(1) and/or Ile(7) in the N-terminal moiety of this mutant peptide allowed full activation of GIPR but not of GLP1R. However, reintroducing Asp(15) and/or His(18) in the central alpha-helical region did not significantly alter the ligand potency. These results suggest that Tyr/His(1) and Ile/Thr(7) of GIP/GLP-1 peptides confer differential ligand selectivity toward GIPR and GLP1R. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | KOREAN SOC MOLECULAR & CELLULAR BIOLOGY | - |
dc.subject | GASTRIC-INHIBITORY POLYPEPTIDE | - |
dc.subject | MOLECULAR EVOLUTION | - |
dc.subject | BIOACTIVE DOMAIN | - |
dc.subject | GLP-1 | - |
dc.subject | EXENDIN-4 | - |
dc.subject | AGONIST | - |
dc.subject | BIOLOGY | - |
dc.subject | BINDING | - |
dc.subject | GENE | - |
dc.subject | CELL | - |
dc.title | Tyr(1) and Ile(7) of Glucose-Dependent Insulinotropic Polypeptide (GIP) Confer Differential Ligand Selectivity toward GIP and Glucagon-like Peptide-1 Receptors | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Hee Young | - |
dc.contributor.affiliatedAuthor | Kim, Sin Gon | - |
dc.contributor.affiliatedAuthor | Choi, Dong Seop | - |
dc.contributor.affiliatedAuthor | Hwang, Jong-Ik | - |
dc.contributor.affiliatedAuthor | Seong, Jae Young | - |
dc.identifier.doi | 10.1007/s10059-010-0100-5 | - |
dc.identifier.scopusid | 2-s2.0-78651485015 | - |
dc.identifier.wosid | 000281384200009 | - |
dc.identifier.bibliographicCitation | MOLECULES AND CELLS, v.30, no.2, pp.149 - 154 | - |
dc.relation.isPartOf | MOLECULES AND CELLS | - |
dc.citation.title | MOLECULES AND CELLS | - |
dc.citation.volume | 30 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 149 | - |
dc.citation.endPage | 154 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.identifier.kciid | ART001470846 | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | GASTRIC-INHIBITORY POLYPEPTIDE | - |
dc.subject.keywordPlus | MOLECULAR EVOLUTION | - |
dc.subject.keywordPlus | BIOACTIVE DOMAIN | - |
dc.subject.keywordPlus | GLP-1 | - |
dc.subject.keywordPlus | EXENDIN-4 | - |
dc.subject.keywordPlus | AGONIST | - |
dc.subject.keywordPlus | BIOLOGY | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | CELL | - |
dc.subject.keywordAuthor | GIP | - |
dc.subject.keywordAuthor | GLP-1 | - |
dc.subject.keywordAuthor | GPCR | - |
dc.subject.keywordAuthor | ligand selectivity | - |
dc.subject.keywordAuthor | insulin | - |
dc.subject.keywordAuthor | pancreas | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.