ACTIVATION OF A NEUROFILAMENT KINASE, A TAU KINASE, AND A TAU PHOSPHATASE BY DECREASED ATP LEVELS IN NERVE GROWTH FACTOR-DIFFERENTIATED PC-12 CELLS

被引:32
作者
BUSH, ML [1 ]
MIYASHIRO, JS [1 ]
INGRAM, VM [1 ]
机构
[1] MIT,DEPT BIOL,CAMBRIDGE,MA 02139
关键词
ALZHEIMER DISEASE; PROTEIN PHOSPHORYLATION; UNCOUPLERS OF OXIDATIVE PHOSPHORYLATION;
D O I
10.1073/pnas.92.6.1861
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Brain pathology in Alzheimer disease and in aged controls shows hyperphosphorylation of tau and of neurofilament proteins. Roder and Ingram [Roder, H.M. & Ingram, V.M. (1991) J. Neurosci. 11, 3325-3343 and Roder, H.M., Eden, P.A. & Ingram, V.M. (1993) Biochem. Biophys. Res. Commun. 193, 639-647] previously reported that the brain protein kinase PK-40(erk) can hyperphosphorylate both tau and neurofilaments and interestingly, is strongly inhibited by ATP uncomplexed with Mg2+. We now report that the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone decreases ATP levels in rat pheochromacytoma (PC-12) cells differentiated with nerve growth factor and activates a neurofilament kinase, a tau kinase, and, unexpectedly, a tau phosphatase-either PP1 or PP2A. Such aberrant modulation of protein phosphorylation patterns could be the common biochemical basis for senile dementia and for Alzheimer disease and could explain the late-onset etiology of both conditions.
引用
收藏
页码:1861 / 1865
页数:5
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