Lew J, Qi Z, Huang Q Q, Paudel H, Matsuura I, Matsushita M, Zhu X, Wang J H
Department of Medical Biochemistry, University of Calgary, Faculty of Medicine, Alberta, Canada.
Neurobiol Aging. 1995 May-Jun;16(3):263-8; discussion 268-70. doi: 10.1016/0197-4580(95)00014-6.
We have identified and purified from bovine brain a novel protein kinase which catalyzes in vitro phosphorylation of neurofilament proteins NF-H and NF-M and tau proteins at sites implicating the enzyme in the regulation of neurocytoskeleton dynamics and in Alzheimer pathology. The protein kinase displays a phosphorylation site specificity similar or identical to the cell cycle regulatory kinase, cdc2 kinase. The purified kinase is a heterodimer of a cdc2-like catalytic subunit, called cdk5, and a 25 kDa regulatory subunit. The regulatory subunit is essential for kinase activity, and it is derived from a 35 kDa protein, p35 by proteolysis. Northern blot analysis of tissue distribution indicates that cdk5 is widely distributed but especially rich in brain, whereas p35 expression is only found in brain. The protein kinase is therefore termed neuronal cdc2-like kinase. The neuron-specificity of the enzyme appears to be conferred by the regulatory subunit. During cell division, cdc2 kinase is regulated by complex phosphorylation mechanisms involving a network of specific protein kinases. Some of these kinases or their homologs have been found in mammalian brains and they may be involved in the regulation of neuronal cdc2-like kinase.
我们已从牛脑中鉴定并纯化出一种新型蛋白激酶，该激酶在体外可催化神经丝蛋白NF-H和NF-M以及tau蛋白在特定位点的磷酸化，这些位点表明该酶参与神经细胞骨架动力学的调节以及阿尔茨海默病的病理过程。该蛋白激酶表现出与细胞周期调节激酶cdc2激酶相似或相同的磷酸化位点特异性。纯化后的激酶是一种异二聚体，由一个类似cdc2的催化亚基（称为cdk5）和一个25 kDa的调节亚基组成。调节亚基对激酶活性至关重要，它是由35 kDa的蛋白p35经蛋白水解衍生而来。组织分布的Northern印迹分析表明，cdk5广泛分布，但在脑中含量尤其丰富，而p35的表达仅在脑中发现。因此，该蛋白激酶被称为神经元cdc2样激酶。该酶的神经元特异性似乎是由调节亚基赋予的。在细胞分裂过程中，cdc2激酶受涉及特定蛋白激酶网络的复杂磷酸化机制调节。其中一些激酶或其同源物已在哺乳动物脑中发现，它们可能参与神经元cdc2样激酶的调节。
