PHOSPHATASE-ACTIVITY TOWARD ABNORMALLY PHOSPHORYLATED-TAU - DECREASE IN ALZHEIMER-DISEASE BRAIN

被引:398
作者
GONG, CX [1 ]
SHAIKH, S [1 ]
WANG, JZ [1 ]
ZAIDI, T [1 ]
GRUNDKEIQBAL, I [1 ]
IQBAL, K [1 ]
机构
[1] NEW YORK STATE INST BASIC RES DEV DISABIL,STATEN ISL,NY 10314
关键词
MICROTUBULE-ASSOCIATED PROTEIN TAU; PROTEIN PHOSPHATASE; PROTEIN DEPHOSPHORYLATION; ALZHEIMER DISEASE;
D O I
10.1046/j.1471-4159.1995.65020732.x
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
Microtubule-associated protein tau is abnormally hyperphosphorylated and aggregated in affected neurons of Alzheimer disease brain. This hyperphosphorylated tau can be dephosphorylated at some of the abnormal phosphorylated sites by purified protein phosphatase-1, 2A, and 2B in vitro. In the present study, we have developed an assay to measure protein phosphatase activity toward tau-1 sites (Ser(199)/Ser(202)) using the hyperphosphorylated tau isolated from Alzheimer disease brain as substrate. Using this assay, we have identified that in normal brain, protein phosphatase-2A and 2B and, to a lesser extent, 1 are involved in the dephosphorylation of tau. The K-m values of dephosphorylation of the hyperphosphorylated tau by protein phosphatase-2A and 2B are similar. The tau phosphatase activity is decreased by similar to 30% in brain of Alzheimer disease patients compared with those of age-matched controls. These findings suggest that a defect of protein phosphatase could be the cause of the abnormal hyperphosphorylation of tau in Alzheimer disease.
引用
收藏
页码:732 / 738
页数:7
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