Abstract 9727920 Turck The regulation of protein function by transient phosphorylation of serine, threonine or tyrosine residues is common in a wide variety of biological processes, including signal transduction events. Phosphorylation of these residues by serine/threonine or tyrosine kinase enzymes can lead to the activation of a protein or promote protein-protein interactions through the newly phosphorylated residue. Histidine kinases mediate the phosphorylation of histidine and have been found to be important in signal transduction in bacteria, yeast and plants. Although phosphohistidine has been observed in mammalian cells the identification and characterization of a histidine kinase has not been reported. Fibroblast growth factor (FGF) activates a histidine kinase in mammalian cells, and this research will characterize and study the function of this histidine kinase in signal transduction events elicited by the fibrobast growth hormone receptor ( FGFR ). The enzyme will be purified and its sequence determined. The cDNA will be cloned and its specificity determined. Recently developed methods for the study of histidine phosphorylation will allow its functional analysis. These studies are designed to begin to understand the significance of histidine phosphorylation in signal transduction in mammalian cells. The phosphorylation of amino acids in proteins by kinase enzymes has been shown to be important in most signal transduction pathways. Kinases are specific for the tyrosine, serine/threonine or histidine residues in proteins. All of these enzymes have been studied in various organisms, however until recently histidine phsophorylation was only found to be important in signaling mechanisms of bacteria, yeast and plants. However it has been found to also occur in mammalian cells. This objective of this research is to purify and characterize a histidine kinase from mammalian cells and study its function. This will be important in our understanding o f the various signal transduction pathways which occur in all organisms. ***
