Manganese and cobalt activate zebrafish ovarian cancer G-protein-coupled receptor 1 but not GPR4

Jun Negishi, Yuka Omori, Mami Shindo, Hayate Takanashi, Shiori Musha, Suminori Nagayama, Jun Hirayama, Hiroshi Nishina, Takashi Nakakura, Chihiro Mogi, Koichi Sato, Fumikazu Okajima, Yuta Mochimaru, Hideaki Tomura

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Mammalian ovarian G-protein-coupled receptor 1 (OGR1) is activated by some metals in addition to extracellular protons and coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebrafish OGR1, zebrafish GPR4, and human GPR4 (zOGR1, zGPR4, and hGPR4, respectively) could sense the metals and activate the intracellular signaling pathways. On one hand, we found that only manganese and cobalt of the tested metals stimulated SRE-promoter activities in zOGR1-overexpressed HEK293T cells. On the other hand, none of the metals tested stimulated the promoter activities in zGPR4- and hGPR4-overexpressed cells. The OGR1 mutant (H4F), which is lost to activation by extracellular protons, did not stimulate metal-induced SRE-promoter activities. These results suggest that zOGR1, but not GPR4, is also a metal-sensing G-protein-coupled receptor in addition to a proton-sensing G-protein-coupled receptor, although not all metals that activate hOGR1 activated zOGR1.

Original languageEnglish
Pages (from-to)401-408
Number of pages8
JournalJournal of Receptor and Signal Transduction Research
Volume37
Issue number4
DOIs
StatePublished - 4 Jul 2017

Keywords

  • GPR4
  • human
  • metal sensing
  • OGR1
  • proton sensing
  • Zebra fish

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