Identification and characterization of mouse metastasis-suppressor KiSS1 and its G-protein-coupled receptor | Academic Article individual record
abstract

G-protein-coupled receptors receive many different signals to activate different functions such as cell growth, 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-β), which suggests direct coupling of the KiSS1 peptide to the Gaαq-mediate PLC-Ca 2+ signaling pathway. Furthermore, activation of the KiSS1 receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis.

authors
author list (cited authors)
Stafford, L. J., Xia, C., Ma, W., Cai, Y., & Liu, M.
publication date
2002
published in
keywords
  • Tumor Suppressor Proteins
  • Kisspeptins
  • Mice
  • Humans
  • Type C Phospholipases
  • Cell Movement
  • Transfection
  • Sequence Homology, Amino Acid
  • GTP-Binding Proteins
  • Animals
  • Amino Acid Sequence
  • Genes, Tumor Suppressor
  • Phospholipase C Beta
  • Cell Division
  • COS Cells
  • Cloning, Molecular
  • Proteins
  • Receptors, Cell Surface
  • Isoenzymes
  • Enzyme Activation
  • 3T3 Cells
  • Molecular Sequence Data
citation count

128