Protein tyrosine phosphorylation is a remarkably conserved mechanism which is implicated in the control of cell growth, differentiation and cell survival in organisms as distantly related as yeast and humans. Although many tyrosine kinases have been described, only recently have protein tyrosine phosphatases (PTPases) been implicated in receptor tyrosine kinase (RTK) mediated signal transduction pathways. The goal of this proposal is to analyze the PTPase, encoded by the Drosophila gene 'corkscrew' (csw), and its role in signal transduction. In addition to csw's putative catalytic activity, it also encodes two SH2 domains, and an SH3 binding concensus sequence, suggesting that 'csw' can mediate heteomeric protein interactions. 'csw' is among the first PTPases whose gene mutations are facilitating a genetic analysis of function in vivo. The structure and function of the 'csw' protein will be investigated. The expression and activity of the 'csw' protein will be analyzed in normal and mutant development. Biochemical and genetic screens will be conducted to identify proteins that interact with 'csw'. These studies will collectively further our understanding of the role of a PTPase, covalently linked to two SH2 domains, in a signal transduction pathway initiated at the membrane by a RTK.
