The major aim of the project is the elucidation of the role of the cAMP """"""""system"""""""" in the development of the cellular slime mold, Dictyostelium discoideum. The cAMP-dependent protein kinase and its catalytic and regulatory subunits will be studied with emphasis on their potential role as triggers for the transitions between different stages of development and for the bifurcation of cellular differentiation into spores and stalk cells. The holoenzyme and its subunits will be characterized with respect to the time course of synthesis, changes in their properties and cellular and subcellular location during development. Comparative studies (in collaboration with another laboratory) of the domains and relevant amino acid sequences of the slime mold and mammalian cAMP-dependent protein kinases are envisaged. Develomental mutants of D. discoideum will be examined for possible defects in the cAMP-dependent protein kinase and new mutants will be selected for abnormalities of the enzyme. Substrates of the cAMP-dependent protein kinase will be characterized with respect to cellular and subcellular location, time of phosphorylation and occurrence in mutants. An attempt will be made to clone the gene which codes for the regulatory subunit of the Dictyostelium cAMP-dependent protein kinase. The health-related significance of the project lies in the central role of cAMP as the cellular mediator of the effects of many hormones and in the relevance of Dictyostelium as a model for the study of development and its abnormalities.
