Goedert M, Jakes R, Qi Z, Wang J H, Cohen P
MRC Laboratory of Molecular Biology, Cambridge, England, U.K.
J Neurochem. 1995 Dec;65(6):2804-7. doi: 10.1046/j.1471-4159.1995.65062804.x.
The paired helical filament (PHF), which makes up the major fibrous component of the neurofibrillary lesions of Alzheimer's disease, is composed of hyperphosphorylated and abnormally phosphorylated microtubule-associated protein tau. Previous studies have identified serine and threonine residues phosphorylated in PHF-tau and have shown that tau can be phosphorylated at several of these sites by proline-directed protein kinases and cyclic AMP-dependent protein kinase. Here we have investigated which protein phosphatase activities can dephosphorylate recombinant tau phosphorylated with mitogen-activated protein kinase, glycogen synthase kinase-3 beta, neuronal cdc2-like kinase, or cyclic AMP-dependent protein kinase. We show that protein phosphatase 2A is by far the major protein phosphatase activity in brain that dephosphorylates tau phosphorylated in this manner.
成对螺旋丝（PHF）构成了阿尔茨海默病神经原纤维病变的主要纤维成分，它由过度磷酸化和异常磷酸化的微管相关蛋白tau组成。先前的研究已确定了PHF-tau中磷酸化的丝氨酸和苏氨酸残基，并表明tau可在其中几个位点被脯氨酸定向蛋白激酶和环磷酸腺苷依赖性蛋白激酶磷酸化。在此，我们研究了哪些蛋白磷酸酶活性能够使被丝裂原活化蛋白激酶、糖原合酶激酶-3β、神经元细胞周期蛋白依赖性激酶2样激酶或环磷酸腺苷依赖性蛋白激酶磷酸化的重组tau去磷酸化。我们发现，蛋白磷酸酶2A是大脑中使以这种方式磷酸化的tau去磷酸化的主要蛋白磷酸酶活性。
