A novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebrates

dc.contributor.authorPark, Cho Rongen_ZA
dc.contributor.authorMoon, Mi Jinen_ZA
dc.contributor.authorPark, Sumien_ZA
dc.contributor.authorKim, Dong-Kyuen_ZA
dc.contributor.authorCho, Eun Beeen_ZA
dc.contributor.authorMillar, Robert Peteren_ZA
dc.contributor.authorHwang, Jong-Iken_ZA
dc.contributor.authorSeong, Jae Youngen_ZA
dc.date.accessioned2016-01-11T06:46:21Z
dc.date.available2016-01-11T06:46:21Z
dc.date.issued2013en_ZA
dc.description.abstractThe glucagon (GCG) peptide family consists of GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from a common GCG precursor, and the glucose-dependent insulinotropic polypeptide (GIP). These peptides interact with cognate receptors, GCGR, GLP1R, GLP2R, and GIPR, which belong to the secretin-like G protein-coupled receptor (GPCR) family. We used bioinformatics to identify genes encoding a novel GCG-related peptide (GCRP) and its cognate receptor, GCRPR. The GCRP and GCRPR genes were found in representative tetrapod taxa such as anole lizard, chicken, and Xenopus , and in teleosts including medaka, fugu, tetraodon, and stickleback. However, they were not present in mammals and zebrafish. Phylogenetic and genome synteny analyses showed that GCRP emerged through two rounds of whole genome duplication (2R) during early vertebrate evolution. GCRPR appears to have arisen by local tandem gene duplications from a common ancestor of GCRPR , GCGR , and GLP2R after 2R. Biochemical ligand-receptor interaction analyses revealed that GCRP had the highest affinity for GCRPR in comparison to other GCGR family members. Stimulation of chicken, Xenopus , and medaka GCRPRs activated Gα s -mediated signaling. In contrast to chicken and Xenopus GCRPRs, medaka GCRPR also induced Gα q/11 -mediated signaling. Chimeric peptides and receptors showed that the K 16 M 17 K 18 and G 16 Q 17 A 18 motifs in GCRP and GLP1, respectively, may at least in part contribute to specific recognition of their cognate receptors through interaction with the receptor core domain. In conclusion, we present novel data demonstrating that GCRP and GCRPR evolved through gene/genome duplications followed by specific modifications that conferred selective recognition to this ligand-receptor pair.en_ZA
dc.identifier.apacitationPark, C. R., Moon, M. J., Park, S., Kim, D., Cho, E. B., Millar, R. P., ... Seong, J. Y. (2013). A novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebrates. <i>PLoS One</i>, http://hdl.handle.net/11427/16222en_ZA
dc.identifier.chicagocitationPark, Cho Rong, Mi Jin Moon, Sumi Park, Dong-Kyu Kim, Eun Bee Cho, Robert Peter Millar, Jong-Ik Hwang, and Jae Young Seong "A novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebrates." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/16222en_ZA
dc.identifier.citationPark, C. R., Moon, M. J., Park, S., Kim, D. K., Cho, E. B., Millar, R. P., ... & Seong, J. Y. (2012). A novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebrates. PloS one, 8(6), e65420. doi:10.1371/journal.pone.0065420en_ZA
dc.identifier.ris TY - Journal Article AU - Park, Cho Rong AU - Moon, Mi Jin AU - Park, Sumi AU - Kim, Dong-Kyu AU - Cho, Eun Bee AU - Millar, Robert Peter AU - Hwang, Jong-Ik AU - Seong, Jae Young AB - The glucagon (GCG) peptide family consists of GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from a common GCG precursor, and the glucose-dependent insulinotropic polypeptide (GIP). These peptides interact with cognate receptors, GCGR, GLP1R, GLP2R, and GIPR, which belong to the secretin-like G protein-coupled receptor (GPCR) family. We used bioinformatics to identify genes encoding a novel GCG-related peptide (GCRP) and its cognate receptor, GCRPR. The GCRP and GCRPR genes were found in representative tetrapod taxa such as anole lizard, chicken, and Xenopus , and in teleosts including medaka, fugu, tetraodon, and stickleback. However, they were not present in mammals and zebrafish. Phylogenetic and genome synteny analyses showed that GCRP emerged through two rounds of whole genome duplication (2R) during early vertebrate evolution. GCRPR appears to have arisen by local tandem gene duplications from a common ancestor of GCRPR , GCGR , and GLP2R after 2R. Biochemical ligand-receptor interaction analyses revealed that GCRP had the highest affinity for GCRPR in comparison to other GCGR family members. Stimulation of chicken, Xenopus , and medaka GCRPRs activated Gα s -mediated signaling. In contrast to chicken and Xenopus GCRPRs, medaka GCRPR also induced Gα q/11 -mediated signaling. Chimeric peptides and receptors showed that the K 16 M 17 K 18 and G 16 Q 17 A 18 motifs in GCRP and GLP1, respectively, may at least in part contribute to specific recognition of their cognate receptors through interaction with the receptor core domain. In conclusion, we present novel data demonstrating that GCRP and GCRPR evolved through gene/genome duplications followed by specific modifications that conferred selective recognition to this ligand-receptor pair. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0065420 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - A novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebrates TI - A novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebrates UR - http://hdl.handle.net/11427/16222 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16222
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0065420
dc.identifier.vancouvercitationPark CR, Moon MJ, Park S, Kim D, Cho EB, Millar RP, et al. A novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebrates. PLoS One. 2013; http://hdl.handle.net/11427/16222.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentMRC/UCT Receptor Biology Research Groupen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2013 Park et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherChickensen_ZA
dc.subject.otherXenopusen_ZA
dc.subject.otherReptile genomicsen_ZA
dc.subject.otherGenome analysisen_ZA
dc.subject.otherMammalian genomicsen_ZA
dc.subject.otherSequence motif analysisen_ZA
dc.subject.otherChromosomesen_ZA
dc.subject.otherVertebratesen_ZA
dc.titleA novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebratesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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