LOCALIZATION AND REGULATION OF THE RAF-1 PROTEIN KINASE

Raf-1是一种丝氨酸/苏氨酸特异性蛋白激酶， 调节细胞生长的信号转导级联反应 各种各样的生长因子。此外，Raf-1可以是 通过截短调节性N-末端致癌激活 域提出的实验将定义Raf-1 N中的这些区域， 与膜稳定结合所必需的末端。 此外，它们将更精确地描绘出 Raf-1 N-末端对于Raf-1活化和调节是必需的。最后， 使用嵌合蛋白，膜定位之间的关系， 和Raf-1激活将进一步详细探讨。成功 该项目的完成将使人们对Raf-1有更深入的了解 信号传导和促有丝分裂级联的调节。新的见解 从这些研究中得到的Raf-1相互作用可能 潜在地被用作设计用于破坏 需要Raf-1激活的信号，即，那些来自致癌Ras的， 激活酪氨酸激酶受体。

Raf-1 is a serine/threonine specific protein kinase centrally positioned on a signal transduction cascade regulating cell growth in response to a diverse array of growth factors. Additionally, Raf-1 can be oncogenically activated by truncation of the regulatory N-terminal domain proposed experiments will define those regions in the Raf-1 N- terminus necessary for stable association with the membrane. Furthermore, they will delineate more precisely the sequences in the Raf-1 N-terminus necessary for Raf-1 activation and regulation. Lastly, using chimeric proteins, the relationship between membrane localization and Raf-1 activation will be explored in further detail. The successful completion of this project will provide a greater understanding of Raf-1 signalling and the modulation of the mitogenic cascade. New insights into Raf-1 interactions resulting from these investigations could potentially be used as targets for therapeutics designed to disrupt signals requiring Raf-1 activation i.e., those from oncogenic Ras and activated tyrosine kinase receptors.