Tyrosine Phosphorylation in Signal Transduction

Our recent work has focused on the elucidation of the mechanisms by which membrane-bound tyrosine kinases transmit signals within the cell. To examine the role of tyrosine phosphorylation, we have employed the following strategy. First, we have utilized antibodies to phosphotyrosine (anti-P.Tyr) to identify candidate substrates of various tyrosine kinases, such as pp60c-src, the CSF-1 receptor, or the platelet-derived growth factor (PDGF) receptor (Piwnica-Worms et al. 1987; Morrison et al. 1988). Second, we have attempted to characterize the biochemical properties of the putative substrates and to determine in what manner these properties are modified by phosphorylation on tyrosine residues (Kaplan et al. 1986, 1987; Piwnica-Worms et al. 1987; Morrison et al. 1988 and in prep.). In this endeavor, we are recapitulating the classic biochemical analysis used to study the effect of kinases on metabolism. The final portion of our work consists of using modern molecular biological strategies to clone the...