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

Cancer Res. 2002 Oct 1;62(19):5399-404.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Division / physiology
  • Cell Movement / physiology
  • Cloning, Molecular
  • Enzyme Activation
  • GTP-Binding Proteins / metabolism
  • GTP-Binding Proteins / physiology*
  • Genes, Tumor Suppressor*
  • Humans
  • Isoenzymes / metabolism
  • Kisspeptins
  • Mice
  • 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

Substances

  • Isoenzymes
  • KISS1 protein, human
  • Kiss1 protein, mouse
  • Kisspeptins
  • Proteins
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins
  • Type C Phospholipases
  • Phospholipase C beta
  • GTP-Binding Proteins