CHELERYTHRINE IS A POTENT AND SPECIFIC INHIBITOR OF PROTEIN-KINASE-C
CHELERYTHRINE IS A POTENT AND SPECIFIC INHIBITOR OF PROTEIN-KINASE-C
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DOI：
10.1016/0006-291x(90)91544-3
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发表时间：
1990-11-15
影响因子：
3.1
通讯作者：
MAFFRAND, JP
中科院分区：
文献类型：
--
作者：
HERBERT, JM;AUGEREAU, JM;MAFFRAND, JP
苯并菲啶生物碱白屈菜红碱是一种有效的，选择性拮抗剂的钙++/磷脂依赖性蛋白激酶（蛋白激酶C：PKC）从大鼠脑。激酶的半数最大抑制发生在0.66 μ M。白屈菜红碱与PKC的催化结构域相互作用，对于磷酸受体（组蛋白IIIS）是竞争性抑制剂（Ki = 0.7 μ M），对于ATP是非竞争性抑制剂。白屈菜红碱对天然PKC及其催化片段的抑制作用相同，但不影响[3 H]-佛波醇12，13二丁酸酯与PKC的结合，这一事实进一步证明了这种作用。白屈菜红碱选择性抑制PKC相比，酪氨酸蛋白激酶，cAMP依赖性蛋白激酶和钙/钙调蛋白依赖性蛋白激酶。白屈菜红碱的体外抗肿瘤活性可能至少部分是由于抑制PKC，因此表明PKC可能是合理设计抗肿瘤药物的模型。
The benzophenanthridine alkaloid chelerythrine is a potent, selective antagonist of the Ca++/phospholopid-dependent protein kinase (Protein kinase C: PKC) from the rat brain. Half-maximal inhibition of the kinase occurs at 0.66 .mu.M. Chelerythrine interacted with the catalytic domain of PKC, was a competitive inhibitor with respect to the phosphate acceptor (histone IIIS) (Ki = 0.7 .mu.M) and a non-competitive inhibitor with respect to ATP. This effect was further evidenced by the fact that chelerythrine inhibited native PKC and its catalytic fragment identically and did not affect [3H]-phorbol 12,13 dibutyrate binding to PKC. Chelerythrine selectively inhibited PKC compared to tyrosine protein kinase, cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase. The potent antitumoral activity of chelerythrine measured in vitro might be due at least in part to inhibition of PKC and thus suggests that PKC may be a model for rational design of antitumor drugs.