Activation of glycogen synthase kinase-3 inhibits protein phosphatase-2A and the underlying mechanisms

被引：58

作者：

Liu, Gong-Ping ^{[1
]}

Zhang, Yao ^{[1
]}

Yao, Xiu-Qing ^{[1
]}

Zhang, Chang-E ^{[1
]}

Fang, Jiang ^{[1
]}

Wang, Qun ^{[1
]}

Wang, Jian-Zhi ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongii Med Coll, Key Lab Neurol Dis Hubei Prov, Dept Pathophysiol, Wuhan 430030, Peoples R China

来源：

NEUROBIOLOGY OF AGING | 2008年 / 29卷 / 09期

基金：

中国国家自然科学基金;

关键词：

glycogen synthase kinase-3 beta; protein phosphatase 2A; I-2(PP-2A);

D O I：

10.1016/j.neurobiolaging.2007.03.012

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

The activity of protein phosphatase-2A (PP-2A) is significantly suppressed in the brain of Alzheimer's disease (AD) patients, but the mechanism is not understood. Here, we found an in vivo association of glycogen synthase kinase 30 (GSK-3 beta) with inhibitor-2 of PP-2A (I-2(PP-2A)). The activation of GSK-3 resulted in accumulation of I-2(PP-IA) with concomitant suppression of PP-2A activity and increases of tau phosphorylation in HEK293, N2a and PC12 cells, while inhibition of GSK-3 caused decreases of I-2(PP-2A) with increased PP-2A activity and decreased tau phosphorylation. A positive correlation between GSK-3 beta and I-2(PP-2A) (R = 0.9158) and a negative correlation between GSK3 beta and PP-2A (R = -0.9166) were detected. GSK-3 activation did not affect I-2(PP-2A) mRNA level, while it increased the mRNA level of a heterogeneous ribonucleoprotein A18 (hnRNP A18). The activation of GSK-3 increased the expression and the activity of proteasome system. It suggests that activation of GSK-3 inhibits PP-2A through up-regulation of I-2(PP-2A) with hnRNP A18-involved mechanism. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：1348 / 1358

页数：11

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