细胞生物学
τ蛋白
激酶
磷酸化
细胞周期蛋白依赖激酶5
葛兰素史克-3
P70-S6激酶1
核糖体s6激酶
生物
化学
微管
蛋白激酶A
阿尔茨海默病
细胞周期蛋白依赖激酶2
蛋白激酶B
内科学
疾病
医学
作者
Jin-Jing Pei,Cecilia Björkdahl,Haiyan Zhang,Xin‐Wen Zhou,Bengt Winblad
标识
DOI:10.3233/jad-2008-14405
摘要
The 70-kDa S6 kinase (p70S6K) is a Ser/Thr (S/T)-directed kinase that plays a crucial role in cell growth, cell differentiation, and cell cycle control. This article presented evidence that supports both toxic and protective roles of p70S6K activity towards tau in Alzheimer's disease (AD) brains. The p70S6K can phosphorylate tau at S262, S214, and T212 sites. Phosphorylation at these sites might release tau from microtubules, resulting in microtubule disruption. Evidence also suggests that p70S6K regulates the translation of tau mRNA by phosphorylating the 40S ribosomal protein S6. The extracellular amyloid-beta deposition in AD brains could be a causative factor that activates p70S6K. We hypothesized that amyloid-beta deposition activates p70S6K whose anti-apoptotic property subsequently keeps neurons from entering into the apoptotic process. This process provides the opportunity for the newly synthesized tau to be phosphorylated by p70S6K and by other tau kinases. This hyperphosphorylated tau then aggregates and is progressively deposited in neurons.
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