A Novel Glucagon-Related Peptide (GCRP) and Its Receptor GCRPR Account for Coevolution of Their Family Members in Vertebrates

Cho Rong Park, Mi Jin Moon, Sumi Park, Dong Kyu Kim, Eun Bee Cho, Robert Peter Millar, Jong-Ik Hwang, Jae Young Seong

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 Gαs-mediated signaling. In contrast to chicken and Xenopus GCRPRs, medaka GCRPR also induced Gαq/11-mediated signaling. Chimeric peptides and receptors showed that the K16M17K18 and G16Q17A18 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.

Original languageEnglish
Article numbere65420
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - 2013 Jun 11

Fingerprint

Peptide Receptors
glucagon
coevolution
Glucagon
Vertebrates
vertebrates
peptides
Peptides
receptors
Genes
Oryzias
Xenopus
Glucagon-Like Peptide 1
glucagon-like peptide 1
Chickens
Gene Duplication
Genome
chickens
genome
Proglucagon

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A Novel Glucagon-Related Peptide (GCRP) and Its Receptor GCRPR Account for Coevolution of Their Family Members in Vertebrates. / Park, Cho Rong; Moon, Mi Jin; Park, Sumi; Kim, Dong Kyu; Cho, Eun Bee; Millar, Robert Peter; Hwang, Jong-Ik; Seong, Jae Young.

In: PLoS One, Vol. 8, No. 6, e65420, 11.06.2013.

Research output: Contribution to journalArticle

Park, Cho Rong ; Moon, Mi Jin ; Park, Sumi ; Kim, Dong Kyu ; Cho, Eun Bee ; Millar, Robert Peter ; Hwang, Jong-Ik ; Seong, Jae Young. / A Novel Glucagon-Related Peptide (GCRP) and Its Receptor GCRPR Account for Coevolution of Their Family Members in Vertebrates. In: PLoS One. 2013 ; Vol. 8, No. 6.
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