Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish

Yuta Mochimaru, Morio Azuma, Natsuki Oshima, Yuta Ichijo, Kazuhiro Satou, Kouhei Matsuda, Yoichi Asaoka, Hiroshi Nishina, Takashi Nakakura, Chihiro Mogi, Koichi Sato, Fumikazu Okajima, Hideaki Tomura

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8 Citations (Scopus)

Abstract

Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as a proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebra fish OGR1 and GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple intracellular signaling pathways and, if so, whether the similar positions of histidine residue, which is critical for sensing protons in mammalian OGR and GPR4, also play a role to sense protons and activate the multiple signaling pathways in the zebra fish receptors. We found that extracellular acidic pH stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1 overexpressed cells and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4 overexpressed cells. The substitution of histidine residues at the 12th, 15th, 162th, and 264th positions from the N-terminal of zOGR1 with phenylalanine attenuated the proton-induced SRE-promoter activities. The mutation of the histidine residue at the 78th but not the 84th position from the N-terminal of zGPR4 to phenylalanine attenuated the proton-induced SRE-promoter activities. These results suggest that zOGR1 and zGPR4 are also proton-sensing G-protein-coupled receptors, and the receptor activation mechanisms may be similar to those of the mammalian receptors.

Original languageEnglish
Pages (from-to)493-499
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume457
Issue number4
DOIs
Publication statusPublished - 20 Feb 2015

Keywords

  • GPR4
  • OGR1
  • Proton sensing
  • Zebra fish

Cite this

Mochimaru, Y., Azuma, M., Oshima, N., Ichijo, Y., Satou, K., Matsuda, K., Asaoka, Y., Nishina, H., Nakakura, T., Mogi, C., Sato, K., Okajima, F., & Tomura, H. (2015). Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish. Biochemical and Biophysical Research Communications, 457(4), 493-499. https://doi.org/10.1016/j.bbrc.2014.12.105