Direct interaction of soluble human recombinant tau protein with Aβ 1–42 results in tau aggregation and hyperphosphorylation by tau protein kinase II

FEBS Letters

Johnston, Jennifer A²  Wang, Zhigang¹  Rank, Kenneth B¹  Sharma, Satish K¹  Evans, David B¹  Bhattacharya, Keshab¹  Pauley, Adele M¹  Fleck, Timothy J¹ 

[1]Pharmacia Corporation, Protein Science, 7240-267-117, Kalamazoo, MI 49007, USA

[2]Elan Pharmaceuticals, South San Francisco, CA, USA

关键词: Neurofibrillary tangle;    Tau protein kinase II;    Alzheimer's disease;    Amyloid Aβ;    Tau;    Phosphorylation;    NFT;    neurofibrillary tangles;    MT;    microtubule;    TPK II;    tau protein kinase II;    TPK I;    tau protein kinase I;    AD;    Alzheimer's disease;    PHF;    paired helical filament;    DTT;    dithiothreitol;    SDS;    sodium dodecyl sulfate;    PAGE;    polyacrylamide gel electrophoresis;    SPA;    scintillation proximity assay;   

DOI  :  10.1016/S0014-5793(02)02376-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We report here that aggregated β-amyloid (Aβ) 1–42 promotes tau aggregation in vitro in a dose-dependent manner. When Aβ-mediated aggregated tau was used as a substrate for tau protein kinase II (TPK II), an 8-fold increase in the rate of TPK II-mediated tau phosphorylation was observed. The extent of TPK II-dependent tau phosphorylation increased as a function of time and Aβ 1–42 concentration, and hyperphosphorylated tau was found to be decorated with an Alzheimer's disease-related phosphoepitope (P-Thr-231). In HEK 293 cells co-expressing CT-100 amyloid precursor protein and tau, the release of Aβ 1–42 from these cells was impaired. Taken together, these in vitro results suggest that Aβ 1–42 promotes both tau aggregation and hyperphosphorylation.

【 授权许可】

Unknown