Cochlioquinone A, an inhibitor of diacylglycerol kinase

The effects of cochlioquinone A, isolated from Drechslera sacchari, were studied in vitro and in vivo. This compound specifically inhibited diacylglycerol kinase activity with Ki = 3.1 microM. The kinetics revealed that cochlioquinone A inhibited diacylglycerol kinase in competition with ATP, and non-competitively with diacylglycerol. The compound inhibited neither protein kinase C, epidermal growth factor receptor-associated protein tyrosine kinase, nor phospholipase C. Cochlioquinone A reduced the concentration of phosphatidic acid in T cell lymphoma with a half maximal concentration of 3 microM, and simultaneously augmented the phosphorylation of 80 kDa protein, a known substrate of protein kinase C. The degree of the phosphorylation of 80 kDa protein in the presence of cochlioquinone A was similar to that in the presence of phorbol myristate acetate (0.1 microgram/ml). These results demonstrate that cochlioquinone A is a specific inhibitor of diacylglycerol kinase, which regulates the activity of protein kinase C.