COCHLIOQUINONE-A, AN INHIBITOR OF DIACYLGLYCEROL KINASE

The effects of cochlioquinone A, isolated from Drechslera sacchari, we re studied in vitro and in vivo. This compound specifically inhibited diacylglycerol kinase activity with Ki=3.1 mu M. The kinetics revealed that cochlioquinone A inhibited diacylglycerol kinase in competition with ATP, and non-competitively with diacylglycerol. The compound inhi bited neither protein kinase C, epidermal growth factor receptor-assoc iated protein tyrosine kinase, nor phospholipase C. Cochlioquinone A r educed the concentration of phosphatidic acid in T cell lymphoma with a half maximal concentration of 3 mu M, and simultaneously augmented t he phosphorylation of 80kDa protein, a known substrate of protein kina se C. The degree of the phosphorylation of 80kDa protein in the presen ce of cochlioquinone A was similar to that in the presence of phorbol myristate acetate (0.1 mu g/ml). These results demonstrate that cochli oquinone A is a specific inhibitor of diacylglycerol kinase, which reg ulates the activity of protein kinase C.