蛋白激酶对τ蛋白阿尔茨海默样磷酸化的调节作用

Modulation of Protein Kinases on an Alzheimer like Phosphorylation of τ.

微管相关蛋白τ的异常磷酸化是阿尔茨海默病（ Ａ Ｄ） 神经原纤维退变的重要机制之一． 研究发现： 酪蛋白激酶１ （ Ｃ Ｋ１） ，ｃ Ａ Ｍ Ｐ 依赖性蛋白激酶（ Ｐ Ｋ Ａ） 和糖原合成酶激酶３ （ Ｇ Ｓ Ｋ３） 均可不同程度催化重组τ蛋白发生磷酸化， 从而不同程度抑制τ蛋白促微管组装的生物学功能． 如果先将τ蛋白与 Ｐ Ｋ Ａ 预温２ ｈ 后再和 Ｇ Ｓ Ｋ３温育， 则发现τ蛋白磷酸化程度比单纯用 Ｇ Ｓ Ｋ３ 处理显著增高， 生物学活性则显著降低， 电镜检测几乎看不见微管形成． 结果提示： Ｐ Ｋ Ａ 和 Ｇ Ｓ Ｋ３ 在τ蛋白的 Ａ Ｄ

Abnormal phosphorylation of microtubule associated protein τ is one of the major mechanism in Alzheimer neurofibrillary degeneration. It was found that casein kinase 1 (CK 1), cyclic AMP dependent protein kinase (PKA) and glycogen synthase kinase 3 (GSK 3) differentially phosphorylate humanτ(τ3L) and thus inhibit its biological activity. Morever, the phosphorylation and inhibition of this activity of τ by GSK 3 is significantly increased if τ is prephosphorylated by PKA. Under this condition, only neglectable microtubles could be seen by electron microscopy . The data suggest that a synergistic role of PKA and GSK 3 might be involved in abnormal phosphorlation and functional inhibition of τ in Alzheimer disease.