Hasegawa M, Jakes R, Crowther R A, Lee V M, Ihara Y, Goedert M
MRC Laboratory of Molecular Biology, Cambridge, UK.
FEBS Lett. 1996 Apr 8;384(1):25-30. doi: 10.1016/0014-5793(96)00271-2.
A monoclonal antibody (AP422) specific for phosphoserine 422 in microtubule-associated protein tau has been produced. It strongly labels paired helical filament (PHF) tau from Alzheimer's disease brain in a phosphorylation-dependent manner. By contrast, AP422 only labels a small fraction of fetal tau and a very small fraction of tau from adult brain. The amount of tau phosphorylated at Ser-422 in normal brain is minor relative to that phosphorylated at sites recognized by other phosphorylation-dependent anti-tau antibodies of known epitope. It follows that AP422 is the most specific anti-tau antibody available for detecting the neurofibrillary lesions of Alzheimer's disease. We also show that Ser-422 in tau is a good in vitro substrate for mitogen-activated protein kinase, but not for glycogen synthase kinase-3 or neuronal cdc2-like kinase.
已经制备出一种针对微管相关蛋白tau中磷酸化丝氨酸422的单克隆抗体（AP422）。它以磷酸化依赖的方式强烈标记来自阿尔茨海默病大脑的双螺旋丝（PHF）tau。相比之下，AP422仅标记一小部分胎儿tau以及来自成人大脑的极少量tau。正常大脑中在Ser-422位点磷酸化的tau量相对于在其他已知表位的磷酸化依赖抗tau抗体所识别位点磷酸化的tau量较少。因此，AP422是可用于检测阿尔茨海默病神经原纤维病变的最特异性抗tau抗体。我们还表明，tau中的Ser-422是丝裂原活化蛋白激酶的良好体外底物，但不是糖原合酶激酶-3或神经元cdc2样激酶的底物。
