Expression cloning and signal transduction pathway of P2U receptor in mammary tumor cells

Biol Signals. 1996 Jan-Feb;5(1):9-21. doi: 10.1159/000109169.

Abstract

Extracellularly applied ATP, UTP and UDP induce a transient increase in the intracellular Ca2+ concentration of mammary cells via a P2U receptor. The P2U receptor in the mammary tumor cell line MMT060562 was cloned and expressed in the human leukemia cell line K-562. The deduced amino acid sequence of the mammary tumor cell P2U receptor was 98% homologous with that of mouse NG108-15 cells. It was a member of the superfamily of GTP-binding-protein-coupled receptors. ATP and UTP induced the increase in the intracellular concentrations of Ca2+ and inositol-1,4,5-trisphosphate in both mammary tumor cells and P2U-receptor-expressed K562 cells. Dose-response curves on the production of inositol-1,4,5-trisphosphate and Ca2+ by ATP and UTP were consistently similar. Injection of GTP enhanced the ATP-induced outward current and injection of GTP gamma S induced a repetitive outward current. Both pertussis and cholera toxins did not affect ATP-induced calcium increase. It was suggested that the P2U receptor coupled with pertussis- and cholera-toxin-insensitive GTP-binding proteins and activated phosphoinositide turnover.

MeSH terms

  • Adenosine Diphosphate Ribose / analogs & derivatives
  • Adenosine Diphosphate Ribose / pharmacology
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Cell Line
  • Cloning, Molecular
  • Cyclic ADP-Ribose
  • DNA, Complementary / analysis
  • Female
  • Fluorescent Dyes
  • Fura-2
  • GTP-Binding Proteins / metabolism
  • Humans
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Leukemia / metabolism
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / metabolism
  • Mice
  • Molecular Sequence Data
  • Phosphatidylinositols / metabolism
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / physiology*
  • Receptors, Purinergic P2Y2
  • Ryanodine / pharmacology
  • Signal Transduction*
  • Suramin / pharmacology
  • Uridine Triphosphate / pharmacology

Substances

  • DNA, Complementary
  • Fluorescent Dyes
  • P2RY2 protein, human
  • P2ry2 protein, mouse
  • Phosphatidylinositols
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y2
  • Cyclic ADP-Ribose
  • Ryanodine
  • Adenosine Diphosphate Ribose
  • Caffeine
  • Suramin
  • Inositol 1,4,5-Trisphosphate
  • Adenosine Triphosphate
  • GTP-Binding Proteins
  • Calcium
  • Fura-2
  • Uridine Triphosphate

Associated data

  • GENBANK/S83099