ABSTRACT
This chapter describes the current state of knowledge of the mechanism of action of phorbol esters. It describes biochemical events that lead to tumor promotion and platelet aggregation. The structural correlations of a large number of tumor-promoting and nontumor-promoting phorbol esters have been studied with respect to their activity as human lymphocyte mitogens. Tetradecanoyl phorbol acetate (TPA) has been shown to enhance interleukin-2 release by lectin-treated human T cells. The ability of phorbol esters to cause aggregation of blood platelets has been studied with a range of structurally distinct compounds. The mechanism of aggregation of blood platelets by structurally distinct phorbol esters has been studied in detail. Although protein kinase C activity is not affected by calmodulin the enzyme is sensitive to calmodulin inhibitors such as chlorpromazines. Protein kinase C phosphorylates a number of cardiac sarcolemma proteins from chicken heart, including phospholamban.
