STUDIES ON PHYSIOLOGICAL FUNCTION OF ZINC ION-DEPENDENT PHOSPHOTYROSINE PROTEIN PHOSPHATASE

锌离子依赖性磷酸酪氨酸蛋白磷酸酶生理功能的研究

• 批准号: 10672073
• 负责人: FUJIMOTO Sadaki
• 金额: $ 1.6万
• 依托单位: Kyoto Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672073/
• 关键词: TYROSINE PHOSPHATASE; ZINC ION; INOSTTOL MONOPHOSPHATASE; BRAIN; LIVER; PHYSIOLOGICAL FUNCTION; INOSTTOL PHOSPHOLIPID METABOLISM; ALZHEIMER; イノシトール-1-ホスファターゼ; 酸性ホスファターゼ; マグネシウムイオン

(1) We have purified two forms, exhibiting molecular weight of approximately 10000 and 62000, of ZnィイD12+ィエD1 -dependent acid phosphatase (ZnィイD12+ィエD1-Apase) from bovine liver. The low-molecular weight (LMW) Zn2+ -APase catalyzed the hydrolysis of myo-inositol-1-phsphate in the presence of 3 mM MgィイD12+ィエD1 at physiological pH, but the high-molecular weight (HMW) enzyme die not. The LMW- ZnィイD12+ィエD1 -Apase of bovine liver was recognized by polyclonal antibodies developed against the ZnィイD12+ィエD1-Apase of bovine brain, but the HMW-AnィイD12+ィエD1APase was not.(2) myo-Inositol monophosphatase from bovine brain exhibited significant hydrolytic activity only on phosphotyrosine among physiological substrates tested in the peresence on ZnィイD12+ィエD1 ions in an acidic environment. The result indicates that myo-inositol monophosphatase exhibits ZnィイD12+ィエD1 -dependent tyrosine phosphatase activity in an acidic environment.(3) The activity and protein level of myo-inositol monophosphatase were in … More vestigated in samples from normal human and Alzhimer's disease (ASD) postmortem brains. In Ad brains myo-inositol monophosphatase activity and its protein level were significantly higher than in control brains. The activity of myo-inositol monophosphatase per enzyme molecule was similar in control and AD brains. These results suggest that myo-inositol monophosphatase is upregulated in AD, probably reflecting compensatory mechanisms concerned with phospholipid metabolism.(4) The distribution of LMW phosphotyrosine protein phosphatase (PTP) in subcellular fractions of rat brain tissue was investigated. The enzyme was abundant in the particulate fraction of nerve endings. LMW-PTP-1 and II were separated from the nerve ending -rich fraction by chromatofocusing. Nerve endings PTP-1 and II were different in molecular weight, isoelectric point and susceptibility to activator and inhibitors. The properties of nerve endings LMW-PTP-1 and II were similar to those of cytosolic LMW-PTP-1 and II. The abundance of LMW-PTP in nerve endings as well as in the cytosol suggests that this enzyme plays an important role in synaptic function. Less

(1)我们从牛肝中纯化了两种分子量约为10000和62000的锌酰D12+锌酰D1 -依赖性酸性磷酸酶（锌酰D12+锌酰D1-Apase）。低分子量（LMW）Zn ~（2+）-AP酶在3 mM Mg ~（2+）D_1_2 + Mg ~（2+）D_1存在下，在生理pH下催化肌醇-1-磷酸水解，而高分子量（HMW）酶则不催化。牛肝LMW-Zn ~（12）+Zn ~（12）D_1-Apase能被牛脑Zn ~（12）+Zn ~（12）D_1-Apase多克隆抗体识别，而HMW-An ~（12）+Zn ~（12）D_1-Apase不能被牛脑Zn ~（12）+Zn ~（12）D_1-Apase多克隆抗体识别。(2)牛脑肌醇单磷酸酶在酸性环境中对Zn ~（2+）~（2结果表明，肌醇单磷酸酶在酸性环境中表现出锌离子D12+锌离子D1依赖的酪氨酸磷酸酶活性。(3)肌醇单磷酸酶的活性和蛋白质水平分别为 ...更多信息 研究了正常人和阿尔茨海默病（ASD）死后大脑的样本。Ad组脑内肌醇单磷酸酶活性及其蛋白水平均显著高于对照组。每酶分子的肌醇单磷酸酶的活性在对照组和AD组大脑中相似。这些结果表明，肌醇单磷酸酶在AD中上调，可能反映了与磷脂代谢有关的代偿机制。(4)本文研究了低分子量磷酸酪氨酸蛋白磷酸酶（PTP）在大鼠脑组织亚细胞组分中的分布。该酶是丰富的神经末梢的颗粒级分。LMW-PTP-1和II通过色谱聚焦从富含神经末梢的级分中分离。神经末梢PTP-1和II在分子量、等电点和对激动剂和抑制剂的敏感性上不同。神经末梢LMW-PTP-1和II的性质与胞浆LMW-PTP-1和II的性质相似。LMW-PTP在神经末梢和细胞质中的丰度表明这种酶在突触功能中起重要作用。少

项目成果

Sadaki Fujimoto, et al.: "myo-Inositol monophosphatase in the brain has zinc ion-dependent tyrosine phosphatase activity"Gen. Pharmac.. 31・3. 469-475 (1998)

Sadaki Fujimoto 等人：“大脑中的肌醇单磷酸酶具有锌离子依赖性酪氨酸磷酸酶活性”Gen. 31・3（1998）。

Junji Tsuda, et al.: "Characterization of high- and low-molecular weight zinc-dependent acid phosphatases in bovine liver"Biol. Pharm. Bull.. 21・11. 1218-1221 (1998)

Junji Tsuda 等：“牛肝脏中高分子量和低分子量锌依赖性酸性磷酸酶的表征”Biol. Bull. 21・11（1998）。

Shun Shimohama, et al.: "Alteration of myo-inositol monophosphatase in Alzheimer's disease brain"Neurosci. Lett.. 245. 159-162 (1998)

Shun Shimohama 等人：“阿尔茨海默病大脑中肌醇单磷酸酶的改变”Neurosci。

Hiroko Tanino, et al.: "Abundance of low molecular weight phosphotyroine protein phosphatase in the nerve-ending fraction in the brain."Biol. Pharm. Bull.. 22・8. 794-798 (1999)

Hiroko Tanino 等人：“大脑神经末梢部分中低分子量磷酸酪氨酸蛋白磷酸酶的丰度”，Biol Pharm. 794-798 (1999)。

Junji Tsuda, et al.: "Characterixzation of high-and low-molecular weight zinc-dependent acid phosphatase in bovine brain"Biol.Pharm. Bull.. 21(11). 1218-1221 (1998)

Junji Tsuda 等人：“牛脑中高分子量和低分子量锌依赖性酸性磷酸酶的特征”Biol.Pharm。