金属イオンの特性を利用したリン酸化タンパク質の特異的認識と検出(誌上シンポジウム)
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概要
- 論文の詳細を見る
Protein phosphorylation is one of the most important post-translational modifications. Organisms utilize this reversible reaction of proteins to control many cellular activities, including signal transduction, apoptosis, gene expression, cell cycle progression, cytoskeletal regulation, and energy metabolism. Abnormal protein phosphorylation is deeply related to carcinogenesis and neuropathogenesis. Methods for monitoring the phosphorylation status of proteins are, thus, very important with respect to the evaluation of diverse biological and pathological processes. Recently, we reported that a dinuclear metal complex of 1, 3-bis [bis (pyridin-2-ylmethyl)-amino] propan-2-olato acts as a novel phosphate-binding tag molecule, Phos-tag, in an aqueous solution under physiological conditions. The Phos-tag has a vacancy on two metal ions that is suitable for the access of a phosphomonoester dianion (R-OPO^<2->_3) as a bridging ligand. The resulting 1:1 phosphate-binding complex, R-OPO^<2->_3-(Phos-tag)^<3+>, has a total charge of +1. A dinuclear zinc (II) complex (Zn^<2+>-Phos-tag) strongly binds to phenyl phosphate dianion (K_d=2.5×10^<-8>M) at a neutral pH. The anion selectivity indexes against SO^<2->_4, CH_3COO^-, Cl^-, and bisphenyl phosphate monoanion at 25℃ are 5.2×10^3, 1.6×10^4, 8.0×10^5, and>2×10^6, respectively. A manganese (II) homologue (Mn^<2+>-Phos-tag) can also capture the R-OPO^<2->_3 anion, such as phosphoserine, phosphotyrosine, and phosphohistidine, at an alkaline pH. By utilizing the Phos-tag molecule and its derivatives, we developed convenient and reliable methods for the detection of phosphorylated proteins. We believe that our Phos-tag technology will result in great progress in phosphoproteomics.
- 社団法人日本薬学会の論文
- 2007-12-01
著者
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木下 英司
広島大学大学院医歯薬学総合研究科医薬分子機能科学研究室
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木下 恵美子
広島大学大学院医歯薬学総合研究科医薬分子機能科学研究室
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小池 透
広島大学大学院医歯薬学総合研究科医薬分子機能科学研究室
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小池 透
広島大学 大学院医歯薬学総合研究科 医薬分子機能科学研究室
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小池 透
広島大院・医歯薬
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木下 英司
広島大学 大学院医歯薬学総合研究科 医薬分子機能科学研究室
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木下 恵美子
広島大学 大学院医歯薬学総合研究科 医薬分子機能科学研究室
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Kinoshita Eiji
Dep. Of Functional Molecular Sci. Graduate School Of Biomedical Sciences Hiroshima Univ. Kasumi 1-2-
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Kinoshita Eiji
First Department Of Internal Medicine School Of Medicine Tokai University
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Kinoshita Eiji
東海大学 第1内科
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Kashiwagi Eiji
Department Of Urology Graduate School Of Medical Sciences Kyushu University
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小池 透
広島大学大学院医学系研究科臨床薬学系専攻
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木下 英司
広島大学大学院医歯薬学総合研究科 薬学専攻創薬科学講座 医薬分子機能科学教室
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Kinoshita Eiji
Tohkai University School Of Medicine Department Of Internal Medicine Cardiology
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Kinoshita Eiji
Department Of Physiology School Of Medicine Hiroshima University
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木下 恵美子
広島大学大学院医歯薬保健学研究院医薬分子機能科学研究室
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木下 英司
広島大学大学院医歯薬保健学研究院医薬分子機能科学研究室
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木下 恵美子
広島大学大学院医歯薬保健学研究院
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木下 英司
広島大学大学院医歯薬保健学研究院
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