Raf kinase activityEPA Grant Number: U914800
Title: Raf kinase activity
Investigators: Reuther, Gary W.
Institution: Duke University Medical Center
EPA Project Officer: Michaud, Jayne
Project Period: January 1, 1995 through January 1, 1996
Project Amount: $102,000
RFA: STAR Graduate Fellowships (1995) Recipients Lists
Research Category: Fellowship - Health , Health Effects , Academic Fellowships
The objectives of this research project are to: (1) examine the nature of the Raf-1 kinase (Raf)/serine kinase (cBcr) complex and its effect on Raf kinase activity; (2) investigate the nature of the Raf/cBcr complex; (3) determine if a kinase/substrate relationship exists between Raf and cBcr; (4) examine the effect of cBcr phosphorylation of 14-3-3 proteins on the ability of these 14-3-3 proteins to activate the Raf kinase; and (5) investigate the role of Raf in Bcr/Abelson (Abl) signaling. The cBcr protein is encoded by the Bcr gene. This gene was discovered by its presence in the Philadelphia (Ph1) chromosome, which is the result of a chromosomal translocation fusing Bcr sequences to sequences of the Abl tyrosine kinase gene. This fusion leads to the synthesis of Bcr/Abl oncoproteins that are implicated in the pathogenesis of chronic myelogenous and acute lymphocytic leukemias. The Abl tyrosine kinase is constitutively active in this chimera, and this activity is required for the transforming capability of Bcr/Abl. The importance of the oligomerization domain, a tyrosine that when phosphorylated provides a binding site for the growth factor receptor-bound-2 (Grb-2) adaptor protein, and a region that interacts with 14-3-3 proteins and SH2 domains. Although these regions of Bcr are required for the full transforming capability of Bcr/Abl, their role in the normal function of cBcr is not known, because the biological function(s) of Bcr has remained elusive.