REGULATION OF RAS DEPENDENT SIGNAL TRANSDUCTION PATHWAYS

RAS是一种进化上保守的小分子GTP酶，在细胞生长和分化的信号传递中发挥作用。致癌的RAS蛋白是RAS的持续激活形式，可引起不适当的细胞增殖，并与大约30%的人类癌症有关。由于RAS在正常和异常生长过程中都起着至关重要的作用，我们实验室的研究重点是阐明RAS依赖的信号转导的相关成分和调控机制。具体地说，我们的研究可以分为三个主要方面：1.丝氨酸/苏氨酸激酶Raf家族的调控。Raf激酶家族在许多信号转导通路中起着重要的中介作用，将激活的酪氨酸激酶和RAS与丝裂原激活的蛋白激酶(MAPK)和MAPK(MKK或MEK)联系起来。我们在这个项目中的目标是研究Raf在生长、发育和肿瘤形成过程中被激活和失活的方式。2.Ras激酶抑制因子(KSR)的功能。在果蝇和线虫中进行的遗传学研究发现，KSR是RAS信号的积极效应者。我们对哺乳动物KSR蛋白的研究旨在确定KSR转导RAS依赖信号的具体机制(S)。果蝇中的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来识别参与RAS依赖的信号转导的新蛋白。

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.