INFECTIOUS DNA FOR ENDOGENOUS RNA TUMOR VIRUS GENES

该项目的总体目标是阐明ras原型的作用。 信号转导通路中的癌基因导致细胞生长和 差异化。尽管RAS蛋白显然在 受体酪氨酸激酶的信号转导， 哺乳动物细胞中RAS的效应因子(S)尚不清楚。 然而，最近利用显性抑制ras突变体(Ras)的研究 我们实验室开发的)为这方面开辟了新的途径 问题，并导致确定了几个潜在目标 对于RAS的作用：Raf蛋白-丝氨酸/苏氨酸激酶，MAP激酶， 翻译因子eIF-4E和磷脂酰胆碱(PC)转换率。个人电脑 水解法特别有趣，因为它是一种常见的 细胞对生长因子的刺激作用，被认为是一种持续的 甘油二酯的来源，它在长期的 反应，如细胞的生长和分化。此外，目前 数据表明，PC水解作用于Raf的上游，这意味着 PC磷脂酶的激活在RAS中起着核心作用 信号通路。因此，我们计划把研究重点放在房协- 依附于PC的水解，根据以下具体目的： 1.PC更替与Raf激活的关系分析 在有丝分裂信号转导过程中。 2.GAP在依赖RAS激活PC-PLC中的作用 和PC12细胞的神经元分化。 3.RAS激活的PC特异性磷脂酶的特性 在有丝分裂信号转导过程中。 4.作为靶点的蛋白激酶C同工酶的鉴定 由PC衍生的二酰基甘油激活。

The overall goal of the project is elucidation of the roles of ras proto- oncogenes in signal transduction pathways leading to cell growth and differentiation. Although Ras proteins clearly play a central role in the transduction of signals from receptor tyrosine kinases, the effector(s) of Ras in mammalian cells have eluded identification. However, recent studies utilizing a dominant inhibitory ras mutant (ras N-17) developed in our laboratory have opened new approaches to this problem and have led to the identification of several potential targets for Ras action: the Raf protein-serine/threonine kinase, MAP kinase, translation factor eIF-4E, and phosphatidylcholine (PC) turnover. PC hydrolysis is of particular interest since it is a common response of cells to growth factor stimulation and is thought to serve as a sustained source of diacylglycerol which plays a critical role in long-term response such as cell growth and differentiation. In addition, current data suggests that PC hydrolysis acts upstream of Raf, implying that activation of a PC phospholipase plays a central role in the Ras signaling pathway. We therefore plan to focus our studies on Ras- dependent PC hydrolysis, according to the following specific aims: 1. Analysis of the relationship between PC turnover and Raf activation during mitogenic signal transduction. 2. Investigation of the role of GAP in Ras-dependent activation of PC-PLC and in neuronal differentiation of PC12 cells. 3. Characterization of the PC-specific phospholipase activated by Ras during mitogenic signaling. 4. Identification of protein kinase C isozyme that serve as targets for activation by PC-derived diacylglycerol.