Ikura Y, Kudo T, Tanaka T, Tanii H, Grundke-Iqbal I, Iqbal K, Takeda M
Department of Neuropsychiatry, Osaka University Medical School, Suita, Japan.
Neuroreport. 1998 Jul 13;9(10):2375-9. doi: 10.1097/00001756-199807130-00041.
The microtubule-associated protein tau is abnormally hyperphosphorylated in Alzheimer's disease (AD) brain. To date, 21 phosphorylated sites of tau have been identified. In the present study the levels of phosphorylation at Ser199/Ser202, Thr231/Ser235, Ser262/Ser356 and Ser396/Ser404 of tau in AD brain homogenate and its 100,000 x g supernatant were determined using radioimmuno-dot-blot assay. In homogenate, Ser199/Ser202 and Ser262/Ser356 were phosphorylated to similar level and were more phosphorylated than Thr231 or Ser396/Ser404. In supernatant, there was no significant difference in phosphorylated tau level among the investigated sites except for Thr231/Ser235 which was least phosphorylated. These results suggest that Ser199/Ser202 and Ser262/Ser356 are major sites of phosphorylation of tau in AD brain.
微管相关蛋白tau在阿尔茨海默病（AD）脑内出现异常的高度磷酸化。迄今为止，已鉴定出tau蛋白的21个磷酸化位点。在本研究中，采用放射免疫斑点印迹法测定了AD脑匀浆及其100,000×g上清液中tau蛋白在Ser199/Ser202、Thr231/Ser235、Ser262/Ser356和Ser396/Ser404位点的磷酸化水平。在匀浆中，Ser199/Ser202和Ser262/Ser356的磷酸化水平相似，且比Thr231或Ser396/Ser404的磷酸化程度更高。在上清液中，除磷酸化程度最低的Thr231/Ser235外，所研究位点的磷酸化tau水平无显著差异。这些结果表明，Ser199/Ser202和Ser262/Ser356是AD脑内tau蛋白的主要磷酸化位点。
