P34CDC2 AND CELL CYCLE CONTROL

在理解和处理的必要组成部分之一， 癌症是关于细胞如何以高度 控制和规范的方式。 在过去的几年里， 我们对于真核细胞如何 周期是有规律的。 在酵母菌和人类等多种多样的物种中， 在结构和功能上都有显著的保守性， 鉴定 这项建议的主题是这些关键细胞周期之一， 调节剂，称为p34 cdc 2的丝氨酸/苏氨酸蛋白激酶， 在整个细胞周期中受到调节。 p34 cdc 2及其几种 已经使用杆状病毒在昆虫细胞中过量产生了调节因子， 表达系统 这些调节因子包括wee 1+基因产物（a 有丝分裂的负调节因子）和细胞周期蛋白A和B（有丝分裂的正调节因子）。 有丝分裂）。 我们发现p34 cdc 2成为 当与wee 1+基因产物共产生时， 昆虫细胞 此外，p34 cdc 2的酪氨酸磷酸化增加， 当细胞周期蛋白也存在时， 这些结果表明， p107 wee 1和cyclin在酪氨酸调节p34 cdc 2中的作用 磷酸化 该提案利用了最近开发的技术， 独特的试剂来详细分析磷酸化和激酶 p34 cdc 2的活性受p107 wee 1和cyclins的调节。 这 信息预计将大大有助于我们了解 细胞周期调控 此外，关于这两个方面的重要信息 控制细胞生长的机制和识别 在致癌转化过程中被破坏的途径可能是 得到了

One of the necessary components in the understanding and treatment of cancer is the knowledge of how cells reproduce themselves in a highly controlled and regulated manner. Within the past few years, tremendous advancements have been made in our understanding of how the eukaryotic cell cycle is regulated. In species as diverse as yeast and man, proteins with remarkable conservation in both structure and function have been identified. The subject of this proposal is one of these key cell-cycle regulators, a serine/threonine protein kinase referred to as p34cdc2 are regulated throughout the cell cycle. p34cdc2 as well as several of its regulators have been overproduced in insect cells using a baculoviral expression system. These regulators include the wee1+ gene product (a negative regulator of mitosis) and cyclins A and B (positive regulators of mitosis). We have made the novel observation that p34cdc2 becomes phosphorylated on tyrosine when co-produced with the wee1+ gene product in insect cells. Further, the tyrosine phosphorylation of p34cdc2 increases dramatically when cyclin is also present. These results suggest a role for both p107wee1 and cyclin in the regulation of p34cdc2 by tyrosine phosphorylation. This proposal utilizes recently developed techniques and unique reagents to analyze in detail how the phosphorylation and kinase activity of p34cdc2 is regulated by p107wee1 and the cyclins. This information is expected to contribute significantly to our understanding of cell cycle control. In addition, important information regarding both the mechanisms that operate to control cell growth and the identification of pathways that are disrupted during oncogenic transformation may be obtained.