title: Manganese and cobalt activate zebrafish ovarian cancer G-protein-coupled receptor 1 but not GPR4.
abstract: 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.
authors.affiliation: a Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture , Meiji University , Kawasaki , Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Negishi
authors.affiliation: a Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture , Meiji University , Kawasaki , Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Omori
authors.affiliation: a Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture , Meiji University , Kawasaki , Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Shindo
authors.affiliation: a Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture , Meiji University , Kawasaki , Japan.
authors.forename: Hayate
authors.initials: H
authors.lastname: Takanashi
authors.affiliation: a Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture , Meiji University , Kawasaki , Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Musha
authors.affiliation: a Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture , Meiji University , Kawasaki , Japan.
authors.forename: Suminori
authors.initials: S
authors.lastname: Nagayama
authors.affiliation: b Department of Developmental and Regenerative Biology , Medical Research Institute, Tokyo Medical and Dental University , Tokyo , Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hirayama
authors.affiliation: b Department of Developmental and Regenerative Biology , Medical Research Institute, Tokyo Medical and Dental University , Tokyo , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishina
authors.affiliation: c Department of Anatomy, Graduate School of Medicine , Teikyo University , Tokyo , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakakura
authors.affiliation: d Laboratory of Signal Transduction, Department of Molecular Medicine , Institute for Molecular and Cellular Regulation, Gunma University , Maebashi , Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Mogi
authors.affiliation: d Laboratory of Signal Transduction, Department of Molecular Medicine , Institute for Molecular and Cellular Regulation, Gunma University , Maebashi , Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.affiliation: e Laboratory of Pathophysiology, Department of Pharmacy, Faculty of Pharmaceutical Sciences , Aomori University , Aomori , Japan.
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
authors.affiliation: a Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture , Meiji University , Kawasaki , Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Mochimaru
authors.affiliation: a Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture , Meiji University , Kawasaki , Japan.|f Institute of Endocrinology, Meiji University , Kawasaki , Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tomura
mesh_terms: D000818:Animals; D003035:Cobalt / Q000494:pharmacology; D000242:Cyclic AMP; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008345:Manganese / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011522:Protons; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: C091670:GPR4 protein, human; C000596877:GPR4 protein, zebrafish; C486281:GPR68 protein, human; D011522:Protons; D043562:Receptors, G-Protein-Coupled; D029961:Zebrafish Proteins; C000596876:gpr68 protein, zebrafish; D003035:Cobalt; D008345:Manganese; D000242:Cyclic AMP
keywords: GPR4; OGR1; Zebra fish; human; metal sensing; proton sensing