Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish.
Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish.
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DOI：
10.1016/j.bbrc.2014.12.105
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发表时间：
2015-02
影响因子：
3.1
通讯作者：
Y. Mochimaru;M. Azuma;N. Oshima;Yuta Ichijo;K. Satou;K. Matsuda;Yoichi Asaoka;H. Nishina;T. Nakakura;C. Mogi;Koichi Sato;F. Okajima;H. Tomura
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文献类型：
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作者：
Y. Mochimaru;M. Azuma;N. Oshima;Yuta Ichijo;K. Satou;K. Matsuda;Yoichi Asaoka;H. Nishina;T. Nakakura;C. Mogi;Koichi Sato;F. Okajima;H. Tomura
哺乳动物卵巢G蛋白偶联受体1（OGR 1）和GPR 4被鉴定为与多种细胞内信号通路偶联的质子敏感G蛋白偶联受体。在本研究中，我们研究了斑马鱼OGR 1和GPR 4同源物（zOGR 1和zGPR 4）是否可以感知质子并激活多种细胞内信号通路，如果是这样，组氨酸残基的相似位置，这是哺乳动物OGR和GPR 4中感知质子的关键，是否也发挥作用，感知质子并激活斑马鱼受体中的多种信号通路。我们发现细胞外酸性pH刺激zOGR 1过表达细胞中的CRE-、SRE-和NFAT-启动子活性，刺激zGPR 4过表达细胞中的CRE-和SRE-但不刺激NFAT-启动子活性。用苯丙氨酸取代zOGR 1 N-末端第12、15、162和264位的组氨酸残基减弱了质子诱导的SRE启动子活性。zGPR 4 N-末端第78位而非第84位的组氨酸残基突变为苯丙氨酸减弱了质子诱导的SRE启动子活性。这些结果表明，zOGR 1和zGPR 4也是质子敏感G蛋白偶联受体，受体激活机制可能与哺乳动物受体相似。
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.