Vandermeeren M, Lübke U, Six J, Cras P
Innogenetics, Ghent, Belgium.
Neurosci Lett. 1993 Apr 16;153(1):57-60. doi: 10.1016/0304-3940(93)90076-w.
Recently, a mitogen activated protein kinase has been implicated in the generation of a phosphorylated paired helical filament (PHF) epitope recognized by the monoclonal antibody AT8. This epitope consists of phosphorylated serines 199 and/or 202 of the human microtubule associated protein tau. Theoretically, aside from abnormal kinase activity, inhibition of phosphatase activity could also be involved in the abnormal phosphorylation status of the microtubule associated protein tau. To investigate this, we incubated LA-N-5 neuroblastoma cells with okadaic acid, a specific inhibitor of phosphatase 2A. We found that incubating neuroblastoma cells with okadaic acid induces the abnormally phosphorylated AT8 epitope. The effect of okadaic acid is time and dose dependent and is reversible. Our findings suggest that phosphatase activity is important in the regulation of the phosphorylation state of tau. Phosphatases may act directly on tau or may influence the activity of mitogen activated protein kinase. Incubation of LA-N-5 neuroblastoma cells with okadaic acid provides a cellular model in which the generation of a well-defined PHF-tau epitope can be investigated.
最近，一种丝裂原活化蛋白激酶与单克隆抗体AT8识别的磷酸化双螺旋丝（PHF）表位的产生有关。该表位由人微管相关蛋白tau的丝氨酸199和/或202磷酸化组成。理论上，除了异常的激酶活性外，磷酸酶活性的抑制也可能与微管相关蛋白tau的异常磷酸化状态有关。为了对此进行研究，我们用冈田酸（一种磷酸酶2A的特异性抑制剂）孵育LA-N-5神经母细胞瘤细胞。我们发现用冈田酸孵育神经母细胞瘤细胞会诱导异常磷酸化的AT8表位。冈田酸的作用具有时间和剂量依赖性且是可逆的。我们的研究结果表明，磷酸酶活性在tau磷酸化状态的调节中很重要。磷酸酶可能直接作用于tau，也可能影响丝裂原活化蛋白激酶的活性。用冈田酸孵育LA-N-5神经母细胞瘤细胞提供了一个细胞模型，在其中可以研究明确的PHF-tau表位的产生。
