PUBLICATION
Two zebrafish G2A homologs activate multiple intracellular signaling pathways in acidic environment
- Authors
- Ichijo, Y., Mochimaru, Y., Azuma, M., Satou, K., Negishi, J., Nakakura, T., Oshima, N., Mogi, C., Sato, K., Matsuda, K., Okajima, F., Tomura, H.
- ID
- ZDB-PUB-151129-1
- Date
- 2016
- Source
- Biochemical and Biophysical Research Communications 469(1): 81-6 (Journal)
- Registered Authors
- Matsuda, Kouhei
- Keywords
- G2A, proton-sensing, zebrafish
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Cycle Proteins/chemistry*
- Cell Cycle Proteins/metabolism*
- HEK293 Cells
- Humans
- Hydrogen-Ion Concentration*
- Intracellular Fluid/chemistry
- Intracellular Fluid/metabolism
- Molecular Sequence Data
- Protein Binding
- Receptors, G-Protein-Coupled/chemistry*
- Receptors, G-Protein-Coupled/metabolism*
- Signal Transduction/physiology*
- Structure-Activity Relationship
- Zebrafish/metabolism*
- PubMed
- 26614909 Full text @ Biochem. Biophys. Res. Commun.
Citation
Ichijo, Y., Mochimaru, Y., Azuma, M., Satou, K., Negishi, J., Nakakura, T., Oshima, N., Mogi, C., Sato, K., Matsuda, K., Okajima, F., Tomura, H. (2016) Two zebrafish G2A homologs activate multiple intracellular signaling pathways in acidic environment. Biochemical and Biophysical Research Communications. 469(1):81-6.
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 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 174(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 32(th) 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 10(th) 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping