RRC ID |
38911
|
著者 |
Ichijo Y, Mochimaru Y, Azuma M, Satou K, Negishi J, Nakakura T, Oshima N, Mogi C, Sato K, Matsuda K, Okajima F, Tomura H.
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タイトル |
Two zebrafish G2A homologs activate multiple intracellular signaling pathways in acidic environment.
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ジャーナル |
Biochem Biophys Res Commun
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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 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.
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巻・号 |
469(1)
|
ページ |
81-86
|
公開日 |
2016-1-1
|
DOI |
10.1016/j.bbrc.2015.11.075
|
PII |
S0006-291X(15)30944-X
|
PMID |
26614909
|
MeSH |
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*
|
IF |
2.985
|
引用数 |
3
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
BIOPHYSICS
|
リソース情報 |
ヒト・動物細胞 |
293T(RCB2202) |