Tau phosphorylated at tyrosine 394 is found in Alzheimer's disease tangles and can be a product of the Abl-related kinase, Arg.
Tau phosphorylated at tyrosine 394 is found in Alzheimer's disease tangles and can be a product of the Abl-related kinase, Arg.
复制标题
DOI：
10.3233/jad-2010-1271
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Davies P
中科院分区：
文献类型：
--
作者：
Tremblay MA;Acker CM;Davies P
Tau是一种微管相关蛋白，是阿尔茨海默病的病理标志之一神经原纤维缠结的主要成分。构成神经原纤维缠结的成对螺旋细丝（PHF）含有一种异常过度磷酸化的tau蛋白。历史上，大多数已被表征的tau磷酸化位点是丝氨酸和苏氨酸残基。最近的报道表明，tau蛋白可以被Fyn、Syk和c-abl （Abl）等激酶磷酸化酪氨酸残基。蛋白质组学分析表明，从阿尔茨海默病大脑中提取的PHF样本中存在酪氨酸394 （Y394）磷酸化的tau蛋白。本研究还通过免疫组织化学证实了Y394磷酸化是阿尔茨海默病的特异性事件。迄今为止，已知只有Abl能够磷酸化tau蛋白上的这个特定位点。我们首次报道，Abl酪氨酸激酶家族的另一个成员Arg也以独立于Abl活性的方式磷酸化tau蛋白的Y394位点。鉴于已报道的Arg在氧化应激反应和神经发育中的作用，Y394磷酸化tau的能力暗示Arg在阿尔茨海默病和其他tau病的发病机制中可能发挥作用。
Tau is a microtubule-associated protein and a main component of neurofibrillary tangles, one of the pathologic hallmarks of Alzheimer’s disease. The paired helical filaments (PHF) that comprise neurofibrillary tangles contain an abnormally hyperphosphorylated form of tau. Historically, most of the tau phosphorylation sites that have been characterized are serine and threonine residues. Recent reports state that tau can be phosphorylated at tyrosine residues by kinases including Fyn, Syk, and c-abl (Abl). Proteomic analyses show that tau phosphorylated at tyrosine 394 (Y394) exists within PHF samples taken from Alzheimer’s disease brains. This study also confirms phosphorylation of Y394 as an Alzheimer’s disease-specific event by immunohistochemistry. To date, only Abl is known to phosphorylate this particular site on tau. We report, for the first time, that Arg, the other member of the Abl family of tyrosine kinases, also phosphorylates tau at Y394 in a manner independent of Abl activity. Given the reported role of Arg in oxidative stress response and neural development, the ability to phosphorylate tau at Y394 implicates Arg as a potential player in the pathogenesis of Alzheimer’s disease and other tauopathies.