摘要
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 K1) ,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 K3) 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 K3温育, 则发现τ蛋白磷酸化程度比单纯用 G S K3 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 K3 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.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
1999年第4期373-375,共3页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金
关键词
蛋白激酶
阿尔茨海默病
Τ蛋白
异常磷酸化
protein kinase, Alzheimer disease, τ protein, abnormal phosphorylation