Identification and characterization of mouse metastasis-suppressor KiSS1 and its G-protein-coupled receptor

• Published in: Cancer research (Chicago, Ill.) Vol. 62; no. 19; pp. 5399 - 5404
• Main Authors: STAFFORD, Lewis Joe, CHUNZHI XIA, WENBIN MA, YI CAI, MINGYAO LIU
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.10.2002
• Subjects: 3T3 Cells; Amino Acid Sequence; Animals; Biological and medical sciences; Cell Division - physiology; Cell Movement - physiology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cloning, Molecular; COS Cells; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Genes, Tumor Suppressor; GTP-Binding Proteins - metabolism; GTP-Binding Proteins - physiology; Humans; Isoenzymes - metabolism; Kisspeptins; Mice; Molecular and cellular biology; Molecular Sequence Data; Phospholipase C beta; Proteins - genetics; Proteins - physiology; Receptors, Cell Surface - metabolism; Receptors, Cell Surface - physiology; Sequence Homology, Amino Acid; Transfection; Tumor Suppressor Proteins; Type C Phospholipases - metabolism; Cell proliferation; Gene product; Migration; Rodentia; Identification; Metastasis; In vitro; Characterization; Signal transduction; Vertebrata; Mammalia; Mouse; Animal; Metastasis suppressor gene; Established cell line; Receptor protein; Mechanism of action; Aminoacid sequence; G protein; Biological receptor
• ISSN: 0008-5472; 1538-7445

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.