Discovery of new drugs depends largely upon random screening directed towards specific enzyme targets. Protein kinase C (PKC), a family of serine/threonine-specific protein kinases, is critical in the control of multiple cellular responses, including gene expression, proliferation, differentiation and tumor promotion, and has thus become a primary target in the development of drug. Despite its enormous therapeutic potential, only a few drug candidates that utilize the PKC pathway have been discovered. Recent advances in molecular biology have paved the way for expression of target isoenzymes of P2KC in insect cells in high yields, which has enabled mass screening of samples. Marine organisms have proven to be a very valuable source of biologically active compounds. However, their potential as a source for new pharmaceuticals is still largely unexplored. The primary goal of the current proposal is to screen extracts derived from marine invertebrates in assays against isoenzymes of protein kinase C. To represent species diversity, the marine organisms are collected from different geographical locations. The long range objectives are to isolate and characterize small organic molecules from these organisms that selectively inhibit or activate protein kinase C isoenzymes and to evaluate their therapeutic potential.