COCHLIOQUINONE-A, AN INHIBITOR OF DIACYLGLYCEROL KINASE
COCHLIOQUINONE-A, AN INHIBITOR OF DIACYLGLYCEROL KINASE
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DOI：
10.7164/antibiotics.48.1076
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发表时间：
1995-10-01
影响因子：
3.3
通讯作者：
OGAWARA, H
中科院分区：
文献类型：
--
作者：
MACHIDA, T;HIGASHI, K;OGAWARA, H
本文研究了从甘蔗Drechslera sacchari中分离得到的Cochlioquinone A的体内、外作用。该化合物特异性抑制二酰基甘油激酶活性，Ki=3.1 μ M。动力学研究表明，辅酶Q A与ATP竞争抑制甘油二酯激酶，与甘油二酯非竞争性抑制。该化合物既不抑制蛋白激酶C、表皮生长因子受体相关蛋白酪氨酸激酶，也不抑制磷脂酶C。Cochlioquinone A降低T细胞淋巴瘤中磷脂酸的浓度，其半最大浓度为3 μ M，同时增强蛋白激酶C的已知底物80 kDa蛋白的磷酸化。80 kDa蛋白质的磷酸化程度与佛波酯（0.1 μ g/ml）的磷酸化程度相似，表明辅酶A是甘油二酯激酶的特异性抑制剂，它调节蛋白激酶C的活性。
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 mu M. 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 mu M, and simultaneously augmented the phosphorylation of 80kDa protein, a known substrate of protein kinase C. The degree of the phosphorylation of 80kDa protein in the presence of cochlioquinone A was similar to that in the presence of phorbol myristate acetate (0.1 mu g/ml).These results demonstrate that cochlioquinone A is a specific inhibitor of diacylglycerol kinase, which regulates the activity of protein kinase C.