title: Identification and characterization of a novel RF-amide peptide ligand for orphan G-protein-coupled receptor SP9155.
abstract: Orphan G-protein-coupled receptors are a large class of receptors whose cognate ligands are unknown. SP9155 (also referred to as AQ27 and GPR103) is an orphan G-protein-coupled receptor originally cloned from a human brain cDNA library. SP9155 was found to be predominantly expressed in brain, heart, kidney, retina, and testis. Phylogenetic analysis shows that SP9155 shares high homology with Orexin, NPFF, and cholecystokinin (CCK) receptors, but identification of the endogenous ligand for SP9155 has not been reported. In this study, we have used a novel method to predict peptides from genome data bases. From these predicted peptides, a novel RF-amide peptide, P52 was shown to selectively activate SP9155-transfected cells. We subsequently cloned the precursor gene of the P52 ligand and characterized the activity of other possible peptides encoded by the precursor. This revealed an extended peptide, P518, which exhibited high affinity for SP9155 (EC50 = 7 nm). mRNA expression analysis revealed that the peptide P518 precursor gene is predominantly expressed in various brain regions, coronary arteries, thyroid and parathyroid glands, large intestine, colon, bladder, testes, and prostate. These results indicate the existence of a novel RF-amide neuroendocrine peptide system, and suggest that SP9155 is likely the relevant G-protein-coupled receptor for this peptide.
authors.affiliation: Department of Discovery Technology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Lin
authors.initials: L
authors.lastname: Luo
authors.forename: Eric L
authors.initials: EL
authors.lastname: Gustafson
authors.forename: Deepmala
authors.initials: D
authors.lastname: Yadav
authors.forename: Maureen
authors.initials: M
authors.lastname: Laverty
authors.forename: Nicholas
authors.initials: N
authors.lastname: Murgolo
authors.forename: Galya
authors.initials: G
authors.lastname: Vassileva
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Laz
authors.forename: Jiang
authors.initials: J
authors.lastname: Behan
authors.forename: Ping
authors.initials: P
authors.lastname: Qiu
authors.forename: Luquan
authors.initials: L
authors.lastname: Wang
authors.forename: Suke
authors.initials: S
authors.lastname: Wang
authors.forename: Marvin
authors.initials: M
authors.lastname: Bayne
authors.forename: Jonathan
authors.initials: J
authors.lastname: Greene
authors.forename: Frederick
authors.initials: F
authors.lastname: Monsma
authors.forename: Fang L
authors.initials: FL
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010802:Phylogeny; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D008024:Ligands; D010455:Peptides; C476582:QRFPR protein, human; C476583:Qrfpr protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins