Journal
FEBS LETTERS
Volume 469, Issue 1, Pages 111-117Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(00)01234-5
Keywords
Tau phosphorylation; protein kinase C delta; regulation of glycogen synthase kinase-3; apoptosis; Alzheimer disease; wortmannin
Funding
- NIA NIH HHS [AG08076] Funding Source: Medline
- NINDS NIH HHS [NS18105] Funding Source: Medline
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The role of the phosphatidylinositol 3-kinase (PI3K) pathway in the hyperphosphorylation of tau was investigated in SY5Y human neuroblastoma cells. Wortmannin, an inhibitor of PI3K, induced transient (after 1 h) activation of glycogen synthase kinase-3 (GSK-3), hyperphosphorylation of 2 and dose-dependent cytotoxicity. However, continuous inactivation of protein kinase (PK) B was observed from 1 to 24 h, suggesting the involvement of protein kinase(s) other than PKB in the phosphorylation and inactivation of GSK-3 after 3 h. In cells treated with wortmannin, PKC delta fragments were observed, and the PKC activity increased after 3 h, whereas treatment of cells with z-DEVD-fmk, an inhibitor of caspase 3, also inhibited fragmentation of PKC delta and induced continuous activation of GSK-3. It is suggested that fragmentation of PKC delta during the process of apoptosis results in the phosphorylation and inactivation of GSK-3 and consequently inhibition of the phosphorylation of tau. (C) 2000 Federation of European Biochemical Societies.
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