Cited 40 times in
Differential regulation of cAMP-mediated gene transcription and ligand selectivity by MC3R and MC4R melanocortin receptors
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 임승길 | - |
dc.date.accessioned | 2016-02-19T11:10:34Z | - |
dc.date.available | 2016-02-19T11:10:34Z | - |
dc.date.issued | 2001 | - |
dc.identifier.issn | 0014-2956 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/142567 | - |
dc.description.abstract | Melanocortins are known to be involved in the regulation of feeding behavior. These hormones mediate their effects through G-protein-coupled receptors by stimulating adenylate cyclase. In this study we describe the functional response of melanocortin 4 receptor (MC4R) and melanocortin 3 receptor (MC3R) in HEK 293T cells, by using a luciferase reporter gene under the transcriptional control of a cAMP-responsive element (CRE) as a monitor of intracellular cAMP levels and cAMP-regulated gene expression. We were able to show that MC4R and MC3R expressed in the human cell line HEK 293T stimulate transcription induced by stimulation with different analogs of α-melanocyte-stimulating hormone (α-MSH) at different levels. In our assay of CRE-mediated gene transcription activity, α-MSH-ND was the most efficient α-MSH analog for MC4R whereas NDP-MSH was the most efficient for MC3R. Changing the His6 residue of α-MSH-ND to Gln or Lys markedly decreased CRE-mediated luciferase activity for MC3R compared with MC4R. On analysis by modeling the receptor–ligand complex by NMR, [Gln6]α-MSH-ND and [Lys6]α-MSH-ND showed different conformational interactions between MC3R and MC4R. Furthermore, the maximum coupling efficiency of MC4R and MC3R to G proteins was different; MC4R showed only 30–50% of the maximum activity induced by MC3R. In total, our results suggest that a differential receptor–ligand interaction is involved and that the relative interactions of MC3R and MC4R with G protein are possibly quantitatively and qualitatively different. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 582~591 | - |
dc.relation.isPartOf | EUROPEAN JOURNAL OF BIOCHEMISTRY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adrenocorticotropic Hormone/analogs & derivatives | - |
dc.subject.MESH | Adrenocorticotropic Hormone/chemistry | - |
dc.subject.MESH | Adrenocorticotropic Hormone/metabolism* | - |
dc.subject.MESH | Amino Acids/chemistry | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Binding Sites | - |
dc.subject.MESH | Blotting, Northern | - |
dc.subject.MESH | CHO Cells | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Cricetinae | - |
dc.subject.MESH | Cyclic AMP/metabolism* | - |
dc.subject.MESH | Gene Expression Regulation* | - |
dc.subject.MESH | Genes, Reporter | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Ligands | - |
dc.subject.MESH | Luciferases/metabolism | - |
dc.subject.MESH | Magnetic Resonance Spectroscopy | - |
dc.subject.MESH | Models, Chemical | - |
dc.subject.MESH | Models, Molecular | - |
dc.subject.MESH | Mutation | - |
dc.subject.MESH | Protein Binding | - |
dc.subject.MESH | Receptor, Melanocortin, Type 3 | - |
dc.subject.MESH | Receptor, Melanocortin, Type 4 | - |
dc.subject.MESH | Receptors, Corticotropin/chemistry | - |
dc.subject.MESH | Receptors, Corticotropin/metabolism* | - |
dc.subject.MESH | Response Elements | - |
dc.subject.MESH | Time Factors | - |
dc.subject.MESH | Transcription, Genetic* | - |
dc.subject.MESH | alpha-MSH/chemistry | - |
dc.subject.MESH | alpha-MSH/metabolism | - |
dc.title | Differential regulation of cAMP-mediated gene transcription and ligand selectivity by MC3R and MC4R melanocortin receptors | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Eun Jin Lee | - |
dc.contributor.googleauthor | Soo-Hyun Lee | - |
dc.contributor.googleauthor | Jin-Won Jung | - |
dc.contributor.googleauthor | Weontae Lee | - |
dc.contributor.googleauthor | Byung Jin Kim | - |
dc.contributor.googleauthor | Kye Won Park | - |
dc.contributor.googleauthor | Sung-Kil Lim | - |
dc.contributor.googleauthor | Chang-Ju Yoon | - |
dc.contributor.googleauthor | Ja-Hyun Baik | - |
dc.identifier.doi | 10.1046/j.1432-1327.2001.01900.x | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A03375 | - |
dc.relation.journalcode | J00808 | - |
dc.identifier.eissn | 0014-2956 | - |
dc.identifier.pmid | 11168397 | - |
dc.identifier.url | http://onlinelibrary.wiley.com/doi/10.1046/j.1432-1327.2001.01900.x/abstract | - |
dc.subject.keyword | cAMP | - |
dc.subject.keyword | G-protein | - |
dc.subject.keyword | melanocortin | - |
dc.subject.keyword | molecular modeling | - |
dc.subject.keyword | obesity | - |
dc.contributor.alternativeName | Lim, Sung Kil | - |
dc.contributor.affiliatedAuthor | Lim, Sung Kil | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 268 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 582 | - |
dc.citation.endPage | 591 | - |
dc.identifier.bibliographicCitation | EUROPEAN JOURNAL OF BIOCHEMISTRY , Vol.268(3) : 582-591, 2001 | - |
dc.identifier.rimsid | 31098 | - |
dc.type.rims | ART | - |
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