P35 IS A NEURAL-SPECIFIC REGULATORY SUBUNIT OF CYCLIN-DEPENDENT KINASE-5

P35 IS A NEURAL-SPECIFIC REGULATORY SUBUNIT OF CYCLIN-DEPENDENT KINASE-5
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DOI:
10.1038/371419a0
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发表时间:
1994-09-29
期刊:
影响因子:
64.8
通讯作者:
HARLOW, E
HARLOW, E
中科院分区:
综合性期刊1区
文献类型:
--
作者:
TSAI, LH;DELALLE, I;HARLOW, E

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细胞周期蛋白依赖性激酶5(Cdk 5)最初是通过其与人Cdc 2(1)的结构同源性分离出来的,Cdc 2是细胞周期进程的关键调节因子(2-6)。在成年小鼠的组织样本中,Cdk 5蛋白在脑中的水平最高,在睾丸中的水平居中,在所有其他组织中的水平较低或检测不到,但脑是唯一显示Cdk 5组蛋白H1激酶活性的组织(7)。在组织培养细胞系中,尽管存在高水平的Cdk 5,但没有发现等同的激酶活性。这提出了Cdk 5调节亚基负责脑中Cdk 5活化的可能性。在这里,我们描述了一个调节亚基Cdk 5称为p35的克隆和表征。p35表现出神经元细胞特异性的表达模式,它在体内与Cdk 5物理结合并激活Cdk 5激酶。p35与哺乳动物细胞周期蛋白不同,因此代表细胞周期蛋白依赖性激酶活性的新型调节亚基。
CYCLIN-dependent kinase 5 (Cdk5) was originally isolated through its structural homology to human Cdc2(1), a key regulator of cell-cycle progression(2-6). In tissue samples from adult mice, Cdk5 protein is found at the highest level in brain, at an intermediate level in testis, and at low or undetectable levels in all other tissues, but brain is the only tissue that shows Cdk5 histone H1 kinase activity(7). No equivalent kinase activity has been found in tissue culture cell lines despite high levels of Cdk5 This raised the possibility that a Cdk5 regulatory subunit was responsible for the activation of Cdk5 in brain. Here we describe the cloning and characterization of a regulatory subunit for Cdk5 known as p35. p35 displays a neuronal cell-specific pattern of expression, it associates physically with Cdk5 in vivo and activates the Cdk5 kinase. p35 differs from the mammalian cyclins and thus represents a new type of regulatory subunit for cyclin-dependent kinase activity.