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P2‐134: PKB plays a central role to tau hyperphosphorylation in intact living cells
Author(s) -
Zhou Xin Wen,
Winblad Bengt,
Wang Jian Zhi,
Pei Jin Jing
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1207
Subject(s) - phosphorylation , protein kinase b , hyperphosphorylation , protein phosphatase 2 , microbiology and biotechnology , chemistry , biology , phosphatase
Background: Microtubule associated protein tau is abnormally hyperphosphorylated in Alzheimer’s disease (AD) and related tauopathies. In order to address how interactions among PKB, GSK3 and PP2A regulate tau phosphorylation. Methods: Plasmid or siRNA of PKB, GSK and PP2A were tranfected into N2a cell for over-expression or blocking respective enzyme. Results: The results showed that the increased GSK3 phosphorylation at S9, over-expression of GSK dramatically increased PKB phosphorylation at S473 and inhibited the exogenous PKB phosphorylation at T308. Over-expression of GSK3 or PKB could activate PP2A catalytic subunit (PP2AC) through down-regulating the PP2AC phosphorylation at Y307. Reversely partial blocking of PKB or GSK did inhibit PP2A activity by increasing its phosphorylation at Y307. Tau phosphorylation at S396 was increased by over-expression of GSK3 or PKB. Tau phosphorylation at S214 was only induced by over-expression of PKB, While partial blocking of GSK decreased tau phosphorylation at S396, partial blocking of PKB was shown to induce increased tau phosphorylation at both S396 and S214 sites. Blocking PP2AC increased PKB phosphorylation selectively at S473, and GSK phosphorylation selectively at S9, and tau phosphorylation selectively at S396. Conclusions: Results from the intact living cells indicated that initial inhibition of PKB may play a critical role in aberrant phosphorylation of tau in AD brains.