INFECTIOUS DNA FOR ENDOGENOUS RNA TUMOR VIRUS GENES

该项目的总体目标是阐明ras proto的作用， 致癌基因在信号转导途径导致细胞生长， 分化 尽管Ras蛋白在细胞内的表达中发挥着重要作用， 受体酪氨酸激酶信号的转导， 哺乳动物细胞中Ras的效应子尚未鉴定。 然而，最近的研究利用显性抑制ras突变体（ras N-17）在我们的实验室开发了新的方法， 问题，并导致确定了几个潜在的目标 对于Ras作用：Raf蛋白-丝氨酸/苏氨酸激酶，MAP激酶， 翻译因子eIF-4 E和磷脂酰胆碱（PC）周转。 PC 水解是特别令人感兴趣的，因为它是 细胞生长因子刺激，并被认为是作为一个持续的 甘油二酯的来源，它在长期 反应，如细胞生长和分化。 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 信号通路 因此，我们计划把我们的研究重点放在拉斯- 根据以下具体目的， 1. PC更新与Raf激活的关系分析 在有丝分裂信号转导过程中。 2. GAP在Ras依赖的PC-PLC激活中的作用研究 以及对PC 12细胞神经元分化的影响。 3. Ras激活的PC特异性磷脂酶的特性 在有丝分裂信号传导过程中。 4.蛋白激酶C同工酶作为靶点的鉴定 通过PC衍生的二酰基甘油活化。

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.