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Article: Identification and characterization of a glucagon receptor from the goldfish Carassius auratus: Implications for the evolution of the ligand specificity of glucagon receptors in vertebrates

TitleIdentification and characterization of a glucagon receptor from the goldfish Carassius auratus: Implications for the evolution of the ligand specificity of glucagon receptors in vertebrates
Authors
Issue Date2004
PublisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.org
Citation
Endocrinology, 2004, v. 145 n. 7, p. 3273-3288 How to Cite?
AbstractThe structural basis of ligand selectivity of G protein-coupled receptors for metabolic hormones has been an area of intense investigation, and yet it remains unresolved. One approach to delineating the mechanism of ligand-receptor interactions is to compare the ligand specificities of receptors expressed in species that emerged at different times within vertebrate evolution. In this paper we describe the isolation, functional, and phylogenetic characterization of the glucagon receptor from the goldfish Carassius auratus (Teleostei, order Cypriniformes), and compare its ligand specificity with that of the homologous rat receptor. Goldfish (gf) glucagon stimulated glucose production in a dose-dependent manner from isolated goldfish hepatocytes, resulting in 5-fold increase at 1 μM. The goldfish glucagon receptor (gfGlucR) shares 56,51,50, and 52% amino acid identities with frog Rana tigrina regulosa, mouse, rat, and human glucagon receptors, respectively. In competitive binding experiments, the recombinant gfGlucR displays high affinity toward goldfish, zebrafish, and human glucagons (IC50 = 0.6, 9, and 13 nM, respectively) but not toward goldfish glucagon-like peptide-1 or human glucagon-like peptide-1 (7-36) amide. Whereas both goldfish and human glucagons stimulated dose-dependent increases in intracellular cAMP through the recombinant gfGlucR, the recombinant rat GlucR interacted only with human glucagon, analogous to the specificity of the previously characterized glucagon receptor from the frog R. tigrina regulosa. Our results demonstrate that the binding pocket of gfGlucR can accommodate a broad range of glucagon structures and that in the frogs and mammals, there is a structural switch to a more restrictive conformation of glucagon receptors.
Persistent Identifierhttp://hdl.handle.net/10722/84788
ISSN
2015 Impact Factor: 4.159
2015 SCImago Journal Rankings: 2.363
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChow, BKCen_HK
dc.contributor.authorMoon, TWen_HK
dc.contributor.authorHoo, RLCen_HK
dc.contributor.authorYeung, CMen_HK
dc.contributor.authorMüller, Men_HK
dc.contributor.authorChristos, PJen_HK
dc.contributor.authorMojsov, Sen_HK
dc.date.accessioned2010-09-06T08:57:07Z-
dc.date.available2010-09-06T08:57:07Z-
dc.date.issued2004en_HK
dc.identifier.citationEndocrinology, 2004, v. 145 n. 7, p. 3273-3288en_HK
dc.identifier.issn0013-7227en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84788-
dc.description.abstractThe structural basis of ligand selectivity of G protein-coupled receptors for metabolic hormones has been an area of intense investigation, and yet it remains unresolved. One approach to delineating the mechanism of ligand-receptor interactions is to compare the ligand specificities of receptors expressed in species that emerged at different times within vertebrate evolution. In this paper we describe the isolation, functional, and phylogenetic characterization of the glucagon receptor from the goldfish Carassius auratus (Teleostei, order Cypriniformes), and compare its ligand specificity with that of the homologous rat receptor. Goldfish (gf) glucagon stimulated glucose production in a dose-dependent manner from isolated goldfish hepatocytes, resulting in 5-fold increase at 1 μM. The goldfish glucagon receptor (gfGlucR) shares 56,51,50, and 52% amino acid identities with frog Rana tigrina regulosa, mouse, rat, and human glucagon receptors, respectively. In competitive binding experiments, the recombinant gfGlucR displays high affinity toward goldfish, zebrafish, and human glucagons (IC50 = 0.6, 9, and 13 nM, respectively) but not toward goldfish glucagon-like peptide-1 or human glucagon-like peptide-1 (7-36) amide. Whereas both goldfish and human glucagons stimulated dose-dependent increases in intracellular cAMP through the recombinant gfGlucR, the recombinant rat GlucR interacted only with human glucagon, analogous to the specificity of the previously characterized glucagon receptor from the frog R. tigrina regulosa. Our results demonstrate that the binding pocket of gfGlucR can accommodate a broad range of glucagon structures and that in the frogs and mammals, there is a structural switch to a more restrictive conformation of glucagon receptors.en_HK
dc.languageengen_HK
dc.publisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.orgen_HK
dc.relation.ispartofEndocrinologyen_HK
dc.rightsEndocrinology. Copyright © The Endocrine Society.-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAnimals-
dc.subject.meshEvolution, Molecular-
dc.subject.meshGoldfish - genetics-
dc.subject.meshReceptors, Glucagon - genetics - metabolism-
dc.titleIdentification and characterization of a glucagon receptor from the goldfish Carassius auratus: Implications for the evolution of the ligand specificity of glucagon receptors in vertebratesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0013-7227&volume=145&issue=7&spage=3273&epage=3288&date=2004&atitle=Identification+and+characterization+of+a+glucagon+receptor+from+the+goldfish+carassius+auratus:+implications+for+the+evolution+of+the+ligand+specificity+of+glucagon+receptors+in+vertebratesen_HK
dc.identifier.emailChow, BKC:bkcc@hku.hken_HK
dc.identifier.emailHoo, RLC:rubyhoo@hkucc.hku.hken_HK
dc.identifier.authorityChow, BKC=rp00681en_HK
dc.identifier.authorityHoo, RLC=rp01334en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1210/en.2003-0597en_HK
dc.identifier.pmid15033912-
dc.identifier.scopuseid_2-s2.0-3042647279en_HK
dc.identifier.hkuros139701en_HK
dc.identifier.hkuros130967-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-3042647279&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume145en_HK
dc.identifier.issue7en_HK
dc.identifier.spage3273en_HK
dc.identifier.epage3288en_HK
dc.identifier.isiWOS:000222043900033-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChow, BKC=7102826193en_HK
dc.identifier.scopusauthoridMoon, TW=7201655084en_HK
dc.identifier.scopusauthoridHoo, RLC=6602369766en_HK
dc.identifier.scopusauthoridYeung, CM=7201354151en_HK
dc.identifier.scopusauthoridMüller, M=7404689227en_HK
dc.identifier.scopusauthoridChristos, PJ=6701752042en_HK
dc.identifier.scopusauthoridMojsov, S=7004216736en_HK

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