Regulation of Ras-Dependent Signal Transduction Pathways

Ras 依赖性信号转导途径的调节

• 批准号: 6763545
• 负责人: DEBORAH K MORRISON
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6763545
• 关键词: Caenorhabditis elegans; Drosophilidae; biological signal transduction; cell growth regulation; enzyme activity; guanosinetriphosphatases; mitogen activated protein kinase

Ras is a small, evolutionarily conserved GTPase that functions in the transmission of signals mediating cell growth and differentiation. Oncogenic Ras proteins, which are consistutively activated forms of Ras, cause inappropriate cell proliferation and are associated with approximately 30% of all human carcinomas. Because Ras plays such a critical role in both normal and abnormal growth processes, our laboratory has focused its research on elucidating the components involved in and the mechanisms regulating Ras-dependent signal transduction. Specifically, our studies can be divided into three main areas: 1. Regulation of the Raf family of serine/threonine kinases. The Raf kinase family serves as a central intermediate in many signaling cascades, functioning to link activated tyrosine kinases and Ras with mitogen activated protein kinase (MAPK) and MAPK kinase (MKK or MEK). Our goal in this project is to examine the means by which Raf becomes activated and inactivated during growth, development, and oncogenesis. 2. Function of Kinase Suppressor of Ras (KSR). KSR was discovered to be a positive effector of Ras signaling by genetic studies performed in Drosophila and C. elegans. Our investigation of the mammalian KSR protein has been to determine the specific mechanism(s) by which KSR functions to transduce Ras-dependent signals.3. Ras signaling pathways in Drosophila. Due to the complex nature of cellular signal transduction, our laboratory has had an ongoing interest in using Drosophila as a model system for studying signaling events. We are currently using this system to identify novel proteins involved in Ras-dependent signal transduction.

Ras是一种小的、进化上保守的GTdR，其在介导细胞生长和分化的信号传递中起作用。致癌性Ras蛋白是Ras的组成性激活形式，引起不适当的细胞增殖，并且与大约30%的人类癌症相关。由于Ras在正常和异常生长过程中起着至关重要的作用，我们实验室的研究重点是阐明Ras依赖的信号转导所涉及的成分和调节机制。具体而言，我们的研究可以分为三个主要方面：1。丝氨酸/苏氨酸激酶的Raf家族的调节。Raf激酶家族在许多信号传导级联中充当中心中间体，起到将活化的酪氨酸激酶和Ras与促分裂原活化蛋白激酶（MAPK）和MAPK激酶（MKK或MEK）连接的作用。我们在这个项目中的目标是研究Raf在生长，发育和肿瘤发生过程中被激活和失活的方式。2. Ras激酶抑制因子（KSR）的功能在果蝇和果蝇中进行的遗传学研究发现KSR是Ras信号传导的正效应子。优美的我们对哺乳动物KSR蛋白质的研究旨在确定KSR对Ras依赖性信号发挥作用的具体机制。果蝇的Ras信号通路。由于细胞信号转导的复杂性，我们的实验室一直有兴趣使用果蝇作为研究信号事件的模型系统。我们目前正在使用这个系统，以确定新的蛋白质参与Ras依赖的信号转导。