Significance of Tau Phosphorylation and Protein Kinase Regulation in the Pathogenesis of Alzheimer Disease
| Autor: | Masatoshi Takeda, Ichiro Tsujio, Toshihisa Tanaka, Takashi Nishikawa, Takashi Kudo, Kazuhiro Shinosaki |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Apoptosis
tau Proteins macromolecular substances Protein Serine-Threonine Kinases Mitogen-activated protein kinase kinase MAP2K7 Phosphatidylinositol 3-Kinases Alzheimer Disease Proto-Oncogene Proteins Tumor Cells Cultured Humans ASK1 c-Raf Phosphorylation Protein kinase A Protein Kinase C MAP kinase kinase kinase biology Cyclin-dependent kinase 2 Protein kinase R Cell biology Isoenzymes Protein Kinase C-delta Psychiatry and Mental health Clinical Psychology Biochemistry biology.protein Geriatrics and Gerontology Proto-Oncogene Proteins c-akt Gerontology |
| Zdroj: | Alzheimer Disease and Associated Disorders. 14:S18-S24 |
| ISSN: | 0893-0341 |
| DOI: | 10.1097/00002093-200000001-00004 |
| Popis: | The role of the phosphatidylinositol-3 kinase pathway in the hyperphosphorylation of tau protein was investigated in cultured cells. Human kidney 293T-cells were cotransfected with tau and glycogen synthase kinase-3 (GSK-3) genes or tau and protein kinase B genes. The phosphorylation of tau protein was increased by cotransfection with GSK-3; however, it was decreased by cotransfection with protein kinase B. Human neuroblastoma SY5Y cells were treated with wortmannin, an inhibitor of phosphatidylinositol-3 kinase, and only transient (after 1 hour) activation of GSK-3 and hyperphosphorylation of tau protein were observed. However, continuous inactivation of protein kinase B was observed, suggesting the involvement of protein kinases other than protein kinase B in the phosphorylation and inactivation of GSK-3 after 3 hours. In cells treated with wortmannin, protein kinase C delta fragments were observed, and the protein kinase C activity increased after 3 hours, whereas treatment of cells with z-DEVD-fmk, an inhibitor of caspase-3, inhibited fragmentation of protein kinase C delta and induced continuous activation of GSK-3. It is suggested that fragmentation of protein kinase C delta during the process of apoptosis results in the phosphorylation and the inactivation of GSK-3. Those data suggest that, in Alzheimer disease, more complicated mechanisms are involved in the process of phosphorylation of tau protein predominantly regulated by P13K pathway. |
| Databáze: | OpenAIRE |
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