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Author Ichijo, Yuta ♦ Mochimaru, Yuta ♦ Azuma, Morio ♦ Satou, Kazuhiro ♦ Negishi, Jun ♦ Nakakura, Takashi ♦ Oshima, Natsuki ♦ Mogi, Chihiro ♦ Sato, Koichi ♦ Matsuda, Kouhei ♦ Okajima, Fumikazu ♦ Tomura, Hideaki
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ACIDIFICATION ♦ ALANINES ♦ AMP ♦ ARGININE ♦ ASPARAGINE ♦ GTP-ASES ♦ HEAVY WATER ♦ HISTIDINE ♦ PH VALUE ♦ RECEPTORS ♦ RESIDUES
Abstract 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 G{sub s}-protein/cAMP/CRE, G{sub 12/13}-protein/Rho/SRE, and G{sub q}-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 174{sup th} 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. - Highlights: • Zebrafish two G2A homologs are proton-sensing receptors. • The signaling pathways activated by the homologs are different. • Histidine residues and basic amino acid residues critical for sensing protons are conserved.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-01-01
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 469
Issue Number 1


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