title: Cochlioquinone A, an inhibitor of diacylglycerol kinase.
abstract: 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.
mesh_terms: D000818:Animals; D000969:Antinematodal Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D016227:Benzoquinones / Q000493:pharmacokinetics / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D019852:Diacylglycerol Kinase; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*
chemical_list: D000969:Antinematodal Agents; D016227:Benzoquinones; C066134:cochlioquinone A; C087469:stemphone; D017853:Phosphotransferases (Alcohol Group Acceptor); D019852:Diacylglycerol Kinase