This award will support collaborative research in developmental biology between Dr. Robert Dottin, Hunter College, City University of New York, and Dr. Michel Veron, Pasteur Institute, Paris, France. The objective of the project is to investigate the mechanisms by which protein kinases and phosphoprotein phosphatases mediate signal transduction in Dictyostelium. Signal transduction refers to the process by which extracell- ular stimulatory molecules, such as peptide hormones, growth factors and neurotransmitters, mediate intracellular events, such as gene induction. In Dictyostelium discoideum, extracellular cAMP activates genes by binding to cell surface receptors. Binding of this agonist activates the synthesis of intracellular messengers. For extracellular cAMP to induce a Dictyostelium gene, activated nuclear regulatory proteins must interact with regulatory regions on DNA. Reversible protein phosphorylation is involved in the activation/inactivation process. Therefore, the two researchers propose to investigate by a molecular genetic approach the role of protein kinases and phosphoprotein phosphatases in the induction of genes by extracellular cAMP. Dr. Veron has focused on the cloning and the expression of the regulatory subunit of cAMP depended kinase. Dr. Dottin and his research group have identified a large number of clones encoding the catalytic subunit of different protein kinases and phosphoprotein phosphatases. Together they propose to characterize these clones to ascertain their potential roles in these signal transduction pathways. These studies will help to define a fundamental process, the mechanisms by which cells respond to their extracellular environments.
