Abstract 9603871 Ota MAP kinase (MAPK) signaling pathways regulate growth and development in vertebrates, Caenorhabditis elegans, Drosophila and the yeast Saccharomyces cerevisiae. Mechanism regulating MAPK pathways are the subject of intensive research, however the inactivation of these pathways is poorly understood. Protein tyrosine phosphatases (PTPs) are negative regulators of these pathways. By genetic techniques this investigator has isolated 2 PTPs that inactivate a stress response MAPK pathway in the yeast S. Cerevesiae. This pathway, known as HOG for high osmolarity glycerol, regulates the response to osmotic stress. One of the aims of this research is to establish the specificity of action of these enzymes for Hog 1. This is important because the identity of protein phosphatases that inactivate MAPKs remains unclear. Another goal of these studies is to identify the mechanisms by which specificity of the phosphatases for MAPKs is achieved. Since multiple MAPK cascades operate in yeast and mammalian cells, mechanisms to ensure signaling specificity must exist. The genes encoding these enzymes will be systematically mutagenized and the effects of these mutants examined in vivo and in vitro. The regulation of these genes will also be studied. These studies will provide a greater understanding of the roles of PTPs in regulating MAPK signaling, and thereby the regulation of growth and development in yeast and mammals. The research of this grant is to study the enzymes that inactivate one of the major signaling pathways in eukaryotic cells. This signaling path involves a series of protein kinases, and these are inactivated by protein phosphatases, the subject of this grant. These studies will provide a better understanding of the regulation of these signaling pathways which are important in growth, development and many other cellular processes. ***
