NEURONAL CDC2-LIKE KINASE - A CDC2-RELATED PROTEIN-KINASE WITH PREDOMINANTLY NEURONAL EXPRESSION
NEURONAL CDC2-LIKE KINASE - A CDC2-RELATED PROTEIN-KINASE WITH PREDOMINANTLY NEURONAL EXPRESSION
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DOI：
10.1073/pnas.89.22.10867
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发表时间：
1992-11-15
影响因子：
11.1
通讯作者：
BATTEY, JF
中科院分区：
文献类型：
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作者：
HELLMICH, MR;PANT, HC;BATTEY, JF
最近的研究已经表明，存在结构和功能上与酵母细胞周期调节激酶cdc 2相关的蛋白激酶家族[Meyerson，M.，Faha，B.，苏湖K.，Harlow，E. & Tsai，L.- H. 03 The Dog of the Dog（1991）定量56，177-186和Meyerson，M.，Enders，G. H、吴角L.，苏湖K.，戈尔卡角，纳尔逊，C.，Harlow，E. & Tsai，L.- H. 11，2909-2917]。cdc 2家族的两个成员，p34 cdc 2（也称为cdk 1）和cdk 2，已在哺乳动物细胞中被鉴定。cdk 1激酶调节从G2期到M期的进程，并且cdk 2激酶已被提出调节从G1期到S期的进程。在这项工作中，我们已经克隆和结构特征的cdc 2激酶家族的第三个成员与58%的氨基酸序列的同一性，小鼠cdk 1和61%的同一性，人类cdk 2。我们称这种激酶为神经元cdc 2样激酶（neuronal cdc 2-like kinase，nc 3），因为与cdk 1或cdk 2相反，nc 3在终末分化的神经元中以高水平表达，不再处于细胞周期中。以前的研究表明[Hisanaga，S.，Kusubata，M.，奥库穆拉E. & Kishimoto，T.（1991）J.Biol.Chem.266，21798-21803和Guan，R. J.，Hall，F. L. & Cohlberg，J. A.等人（1992）J. Neurochem. 58，1365-1371] cdk 1激酶，而不是其它结构确定的蛋白激酶，可以在体外磷酸化在哺乳动物高和中分子量神经丝亚基中发现的重复的Lys-Ser-Pro（KSP）基序，但是内源性神经元KSP激酶的精确分子性质仍然不确定。的结构相似性的nck 1激酶和其在终末分化的神经元中的高水平的表达表明，nck 1在体内的神经丝KSP重复的磷酸化可能发挥作用，从细胞周期调控不同的功能。
Recent studies have shown that there exists a family of protein kinases structurally and functionally related to the yeast cell cycle regulatory kinase cdc2 [Meyerson, M., Faha, B., Su, L.-K., Harlow, E. & Tsai, L.-H. (1991) Cold Spring Harbor Symp. Quant. Biol. 56, 177-186 and Meyerson, M., Enders, G. H., Wu, C.-L., Su, L.-K., Gorka, C., Nelson, C., Harlow, E. & Tsai, L.-H. (1992) EMBO J. 11, 2909-2917]. Two members of cdc2 family, p34cdc2 (also named cdk1) and cdk2, have been identified in mammalian cells. cdk1 kinase regulates the progression from G2 to M phase, and cdk2 kinase has been proposed to regulate the progression from G1 to S phase. In this work, we have cloned and structurally characterized a third member of the cdc2 kinase family with 58% amino acid sequence identity to mouse cdk1 and 61% identity to human cdk2. We call this kinase neuronal cdc2-like kinase (nclk) because, in contrast to either cdk1 or cdk2, nclk is expressed at high levels in terminally differentiated neurons no longer in the cell cycle. Previous studies have shown [Hisanaga, S., Kusubata, M., Okumura, E. & Kishimoto, T. (1991) J. Biol. Chem. 266, 21798-21803 and Guan, R. J., Hall, F. L. & Cohlberg, J. A. (1992) J. Neurochem. 58, 1365-1371] that cdk1 kinase, but not other structurally defined protein kinases, could phosphorylate the repeated Lys-Ser-Pro (KSP) motifs found in mammalian high and middle molecular mass neurofilament subunits in vitro, but the precise molecular nature of the endogenous neuronal KSP kinase has remained undefined. The structural similarity of nclk to cdk1 kinase and its high level of expression in terminally differentiated neurons suggest that nclk may play a role in the phosphorylation of the neurofilament KSP repeats in vivo, a function distinct from cell cycle regulation.