Phosphorylation of tau protein by purified p34cdc28 and a related protein kinase from neurofilaments.
Phosphorylation of tau protein by purified p34cdc28 and a related protein kinase from neurofilaments.
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DOI：
10.1016/s0021-9258(18)41832-7
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发表时间：
1992-09
期刊：
影响因子：
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通讯作者：
M. Mawal-Dewan;P. Sen;M. Abdel-Ghany;D. Shalloway;E. Racker
中科院分区：
文献类型：
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作者：
M. Mawal-Dewan;P. Sen;M. Abdel-Ghany;D. Shalloway;E. Racker
已有研究表明，神经原纤维缠结中tau蛋白的过度磷酸化可能与阿尔茨海默病的病因有关，并且至少有一个过度磷酸化的位点存在于p34cdc2/cdc28蛋白家族的共同序列中。我们介绍了一种从酿酒酵母中大规模纯化p34cdc28激酶的新方法，并证明了纯化的酶能磷酸化牛和人tau。碱性和酸性底物调节剂的加入极大地促进了磷酸化。衬底调制器的作用因衬底的结构和调制器的不同而不同。用p13su1亲和层析从神经细丝中纯化的一种激酶也得到了类似的结果，这是p34cdc2/cdc28型激酶的标志。这些结果与这种类型的激酶参与了体内tau磷酸化的假设是一致的，并开启了阿尔茨海默病过度磷酸化可能由底物调节剂控制的可能性。
It has been suggested that hyperphosphorylation of the tau protein in neurofibrillary tangles may be relevant to the etiology of Alzheimer's disease and that at least one of the hyperphosphorylated sites lies within a consensus sequence for the p34cdc2/cdc28 family of kinases. We describe a new method for large-scale purification of p34cdc28 kinase from Saccharomyces cerevisiae and show that the purified enzyme can phosphorylate bovine and human tau. Phosphorylation was greatly enhanced by the addition of basic and acidic substrate modulators. The effect of the substrate modulators differed both with the structures of the substrates and the modulators. Similar results were obtained with a kinase that could be purified from neurofilaments by p13suc1 affinity chromatography, a hallmark of p34cdc2/cdc28-type kinases. These results are consistent with the hypothesis that a kinase of this type is involved in tau phosphorylation in vivo and open the possibility that hyperphosphorylation in Alzheimer's disease may be controlled by substrate modulators.