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.