Two zebrafish G2A homologs activate multiple intracellular signaling pathways in acidic environment

Yuta Ichijo, Yuta Mochimaru, Morio Azuma, Kazuhiro Satou, Jun Negishi, Takashi Nakakura, Natsuki Oshima, Chihiro Mogi, Koichi Sato, Kouhei Matsuda, Fumikazu Okajima, Hideaki Tomura*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

3 被引用数 (Scopus)

抄録

Human G2A is activated by various stimuli such as lysophosphatidylcholine (LPC), 9-hydroxyoctadecadienoic acid (9-HODE), and protons. The receptor is coupled to multiple intracellular signaling pathways, including the Gs-protein/cAMP/CRE, G12/13-protein/Rho/SRE, and Gq-protein/phospholipase C/NFAT pathways. In the present study, we examined whether zebrafish G2A homologs (zG2A-a and zG2A-b) could respond to these stimuli and activate multiple intracellular signaling pathways. We also examined whether histidine residue and basic amino acid residue in the N-terminus of the homologs also play roles similar to those played by human G2A residues if the homologs sense protons. We found that the zG2A-a showed the high CRE, SRE, and NFAT activities, however, zG2A-b showed only the high SRE activity under a pH of 8.0. Extracellular acidification from pH 7.4 to 6.3 ameliorated these activities in zG2A-a-expressing cells. On the other hand, acidification ameliorated the SRE activity but not the CRE and NFAT activities in zG2A-b-expressing cells. LPC or 9-HODE did not modify any activity of either homolog. The substitution of histidine residue at the 174th position from the N-terminus of zG2A-a to asparagine residue attenuated proton-induced CRE and NFAT activities but not SRE activity. The substitution of arginine residue at the 32nd position from the N-terminus of zG2A-a to the alanine residue also attenuated its high and the proton-induced CRE and NFAT activities. On the contrary, the substitution did not attenuate SRE activity. The substitution of the arginine residue at the 10th position from the N-terminus of zG2A-b to the alanine residue also did not attenuate its high or the proton-induced SRE activity. These results indicate that zebrafish G2A homologs were activated by protons but not by LPC and 9-HODE, and the activation mechanisms of the homologs were similar to those of human G2A.

本文言語英語
ページ(範囲)81-86
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
469
1
DOI
出版ステータス出版済み - 2016/01/01

ASJC Scopus 主題領域

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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