Gong C X, Grundke-Iqbal I, Damuni Z, Iqbal K
New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314.
FEBS Lett. 1994 Mar 14;341(1):94-8. doi: 10.1016/0014-5793(94)80247-5.
Microtubule-associated protein tau is abnormally hyperphosphorylated and forms the major protein subunit of paired helical filaments (PHF) in Alzheimer disease brains. The abnormally phosphorylated sites Ser-199, Ser-202, Ser-396 and Ser-404 but not Ser-46 and Ser-235 of Alzheimer tau were found to be dephosphorylated by protein phosphatase-1 and this dephosphorylation was activated by Mn2+. In contrast, protein phosphatase-2C did not dephosphorylate any of these sites. Both protein phosphatase-1 and -2C had high activities towards [32P]tau phosphorylated by cAMP-dependent protein kinase. These results suggest that both protein phosphatase-1 and -2C might be associated with normal phosphorylation state of tau, but only the former and not the latter phosphatase is involved in its abnormal phosphorylation in Alzheimer disease.
微管相关蛋白tau在阿尔茨海默病大脑中异常过度磷酸化，并形成双螺旋丝（PHF）的主要蛋白质亚基。研究发现，阿尔茨海默病tau蛋白异常磷酸化位点Ser-199、Ser-202、Ser-396和Ser-404而非Ser-46和Ser-235可被蛋白磷酸酶-1去磷酸化，且这种去磷酸化作用被Mn2+激活。相比之下，蛋白磷酸酶-2C不能使这些位点中的任何一个去磷酸化。蛋白磷酸酶-1和-2C对由cAMP依赖性蛋白激酶磷酸化的[32P]tau均具有高活性。这些结果表明，蛋白磷酸酶-1和-2C可能都与tau的正常磷酸化状态有关，但在阿尔茨海默病中，只有前者而非后者的磷酸酶参与其异常磷酸化过程。
