9357009 Simon Protein tyrosine kinases (PTKs) are important regulatory molecules that control many aspects of cellular growth, differentiation and metabolism. This work is directed toward understanding the mechanisms by which these proteins, particularly those which span the plasma membrane and are controlled by extracellular ligands, regulate intracellular events. The PI has focused his studies on the action of a particular transmembrane PTK that is encoded by the sevenless gene of Drosphilia melanogaster. Mutations that inactivate the sevenless protein (Sev) lead to a single known defect in the fly. Seven Enhancer of sevenless loci were identified. Mutations in four of the Enhancer of sevenless loci also affect signaling by other receptor PTKs. The PI has concentrated on the analysis of these four loci in hopes that they would encode components of a general PTK signaling pathway. One locus, Ras1, encodes a ras protein. ras proteins are known to be molecular switches that control many aspects of cellular activity. How Ras1 is activated has therefore become the crucial question which will be a major focus of this work. %%% This work explores a complex signal transduction system that functions in cellular and organizational development and growth control. Since the components of this system are highly conserved during evolution, it is likely that this knowledge gained will apply to all PTK signalling systems.
