Manganese and cobalt activate zebrafish ovarian cancer G-protein-coupled receptor 1 but not GPR4.
Manganese and cobalt activate zebrafish ovarian cancer G-protein-coupled receptor 1 but not GPR4.
复制标题
锰和钴激活斑马鱼卵巢癌 G 蛋白偶联受体 1，但不激活 GPR4。
DOI：
10.1080/10799893.2017.1298130
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
H. Tomura
中科院分区：
文献类型：
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作者：
J. Negishi;Y. Omori;M. Shindo;H. Takanashi;S. Musha;S. Nagayama;J. Hirayama;H. Nishina;T. Nakakura;C. Mogi;K. Sato;F. Okajima;Y. Mochimaru;H. Tomura
哺乳动物卵巢G蛋白偶联受体1(OGR1)除被细胞外质子激活外，还被多种金属激活，并与多种细胞内信号通路偶联。在本研究中，我们研究了斑马鱼OGR1、斑马鱼GPR4和人GPR4(分别为zOGR1、zGPR4和hGPR4)是否能够感知金属并激活细胞内信号通路。一方面，我们发现只有被测试的金属中的锰和钴在zOGR1过表达的HEK293T细胞中刺激了SRE启动子的活性。另一方面，在zGPR4-和hGPR4-过表达的细胞中，测试的金属都没有刺激启动子的活性。不能被胞外质子激活的OGR1突变体(H4F)不能刺激金属诱导的SRE启动子活性。这些结果表明，除了质子敏感的G蛋白偶联受体外，zOGR1也是一种金属敏感的G蛋白偶联受体，但不是GPR4，尽管并不是所有的金属都能激活hOGR1激活zOGR1。
Mammalian ovarian G-protein-coupled receptor 1 (OGR1) is activated by some metals in addition to extracellular protons and coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebrafish OGR1, zebrafish GPR4, and human GPR4 (zOGR1, zGPR4, and hGPR4, respectively) could sense the metals and activate the intracellular signaling pathways. On one hand, we found that only manganese and cobalt of the tested metals stimulated SRE-promoter activities in zOGR1-overexpressed HEK293T cells. On the other hand, none of the metals tested stimulated the promoter activities in zGPR4- and hGPR4-overexpressed cells. The OGR1 mutant (H4F), which is lost to activation by extracellular protons, did not stimulate metal-induced SRE-promoter activities. These results suggest that zOGR1, but not GPR4, is also a metal-sensing G-protein-coupled receptor in addition to a proton-sensing G-protein-coupled receptor, although not all metals that activate hOGR1 activated zOGR1.