Identification and characterization of mouse metastasis-suppressor KiSS1 and its G-protein-coupled receptor.
G-protein-coupled receptors receive many different signals to activate different functions such as cellgrowth, proliferation, and migration. KiSS1 is a metastasis suppressor gene that has been shown to inhibit metastasis of human melanomas and breast carcinomas. The human KiSS1 gene encodes a COOH-terminally amidated active peptide, and this peptide is the ligand of a novel G-protein-coupled receptor. However, the mechanism of the antimetastatic actions of KiSS1 and its G-protein-coupled receptor has not been elucidated. In this study, we identified the mouse homologues of the KiSS1 peptide and its G-protein-coupled receptor and characterized the signaling pathways mediated by the activation of the KiSS1 receptor. Although human and mouse KiSS1 proteins share relatively low overall homology (52%), the active peptides (10-amino-acid residues) are highly conserved between mouse and human KiSS1 proteins, varying by only one conserved amino acid [Tyr (Y) to Phe (F)]. Activation of the receptor by KiSS1 peptide leads to the activation of G-protein-activated phospholipase C (PLC-beta), which suggests direct coupling of the KiSS1 peptide to the Galphaq-mediate PLC-Ca2+ signaling pathway. Furthermore, activation of the KiSS1 receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis.
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003001:Cloning, Molecular; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D059648:Kisspeptins; D051379:Mice; D008969:Molecular Sequence Data; D054799:Phospholipase C beta; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D025521:Tumor Suppressor Proteins; D010738:Type C Phospholipases / Q000378:metabolism
D007527:Isoenzymes; C106628:KISS1 protein, human; C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D011506:Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins