Inhibitors of protein phosphatase-2A from human brain structures, immunocytological localization and activities towards dephosphorylation of the Alzheimer type hyperphosphorylated tau

被引：72

作者：

Tsujio, I ^{[1
]}

Zaidi, T ^{[1
]}

Xu, JL ^{[1
]}

Kotula, L ^{[1
]}

Grundke-Iqbal, I ^{[1
]}

Iqbal, K ^{[1
]}

机构：

[1] New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA

来源：

FEBS LETTERS | 2005年 / 579卷 / 02期

关键词：

Alzheimer disease; abnormally hyperphosphory- lated tau; protein phosphatase-2A inhibitor; template activating factor; PHAP; LANP;

D O I：

10.1016/j.febslet.2004.11.097

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Protein phosphatase (PP)-2A, which regulates the phosphorylation of tau, is regulated by two endogenous inhibitor proteins, I-1(PP2A) and I-2(PP2A) in mammalian tissues. Here, we report the cloning of I-1(PP2A) and I-2(PP2A) from human brain, and show that in PC12 cells and in I-1(PP2A) - GFP or I-2(PP2A) - GFP transfected NIH3T3 and human neural progenitor cells, I-1(PP2A) is localized mostly in the cell cytoplasm and I-2(PP2A) mostly in the nucleus. The recombinant I-1(PP-2A) and I-2(PP-2A) inhibit PP-2A activity towards hyperphosphorylated tau in vitro; the dephosphorylation of the hyperphosphorylated tau at specific sites is selectively inhibited. Overexpression of I-1(PP2A) as well as I-2(PP2A) results in tau hyperphosphorylation and degeneration of PC12 cells. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：363 / 372

页数：10

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