CDC2-LIKE KINASES IN NORMAL AND MALIGNANT CELLS

最近的研究表明，哺乳动物中存在一个蛋白质家族 蛋白激酶与酵母细胞周期的结构和功能相关 调节激酶CDC-2。Cdc2家族的两个成员，p34/cdc2和 CDK2，已在哺乳动物细胞中被鉴定。P34/cdc2激酶调节 从G2到M的过程，以及CDK2被认为是为了调节 从Gl到S阶段的进展(有关回顾，请参阅Pines and Hunter，Trends 细胞生物。2：72-76,1992)。我们已经克隆并在结构上 鉴定了cdc2蛋白家族的第三个成员，其氨基酸含量为58% 与小鼠p34/cdc2的氨基酸序列同源性和与人CDK2的60%同源性 (作为参考，p34/cdc2和cdk2含有约60%的氨基酸 身份)。这种新的激酶被称为神经元cdc2样激酶(n-clk)。 因为，与p34/cdc2或cdk2不同，n-clk在 终末分化神经元中的高水平。此外，许多人 培养的细胞株表达高水平的n-clk和p34/cdc2 和CDK2激酶。我们计划探索n-CLK在细胞周期中的作用 有丝分裂活性细胞和人类肿瘤的调节，以确定是否 N-CLK是一种潜在的特异性激酶抑制剂的治疗靶点。 此外，还将继续努力开发便利的传播媒介。 药物或小肽与调节性物质相互作用的研究 N-CLK的区域。这项研究将以类似的努力进行。 研究对细胞周期进程很重要的激酶，包括 调节p34/cdc2的p34/cdc2、MAP和G1p34蛋白 活动。

Recent studies have shown that there exists a family of mammalian protein kinases structurally and functionally related to the yeast cell cycle regulatory kinase cdc-2. Two members of the cdc2 family, p34/cdc2 and cdk2, have been identified in mammalian cells. p34/cdc2 kinase regulates the progression from G2 to M, and cdk2 has been proposed to regulate the progression from Gl to S phase (for review, see Pines and Hunter, Trends Cell Biol. 2: 72-76, 1992). We have cloned and structurally characterized a third member of the cdc2 kinase family with 58% amino acid sequence identity to mouse p34/cdc2 and 60% identity to human cdk2 (as a point of reference, p34/cdc2 and cdk2 have about 60% amino acid identity). The new kinase is called neuronal cdc2-like kinase (n-clk) because, in contrast to either p34/cdc2 or cdk2, n-clk is expressed at high levels in terminally differentiated neurons. Moreover, many cultured cell lines express high levels of n-clk mRNA as well as p34/cdc2 and cdk2 kinase. We plan to explore the role of n-clk in cell cycle regulation of mitotically active cells and human tumors, to determine if n-clk is a potential therapeutic target for specific kinase inhibitors. In addition, efforts will continue to develop convenient vectors for studying the interaction of drugs or small peptides with regulatory regions of n-clk. This study will proceed with analagous efforts studying kinases clearly important to cell cycle progression including p34/cdc2 kinase, MAP kinases and Gl p34 kinases which regulate p34/cdc2 activity.