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.
