9400424 Wadzinski Normal signal transduction from the cell surface traversing the cytoplasm and to the nucleus in response to an external stimulus requires pathways which are acutely regulated by the phosphorylation and dephosphorylation of specific proteins. Activation of most cell-surface receptors initially results in the generation of second messenger or stimulation of a protein tyrosine kinase. This signal, however, is rapidly converted via a protein kinase network into activated protein serine/threonine kinases. Many of these kinases have been studied extensively, but much less attention has been given to the reverse reaction catalyzed by specific serine/threonine (ser/thr) protein phosphatases (PP). Furthermore, the majority of studies of these signal transduction pathways studies have focused on cytoplasmic events even though the concentration of phospho-proteins in the nucleus is thought to be much higher than in the cytosol. The importance of protein phosphatases, especially nuclear protein phosphatases, in the control of cell phenotype, growth and differentiation is just now being appreciated. The long term goals of this research are to define the subcellular distribution of phosphatases, characterize specific nuclear phosphatases, identify specific nuclear phosphatase substrates, define the regulation of protein phosphatases, and to define regulatory and effector sites of protein phosphatase catalytic subunits using a mutagenesis approach. %%% This is a starter grant to help set up the laboratory and launch the independent career of a promising new investigator who, for the past two years, has been supported by an NSF Post-Doctoral Fellowship. The overall goal of his research is to study the function and regulation of certain enzymes, called protein phosphatases, in signal transduction pathways of cells. The long term results of this research will contribute to our fundamental understanding of the regulation of cellular function. ***
