Contrasting actions of staurosporine, a protein kinase C inhibitor, on human neutrophils and primary mouse epidermal cells.
Contrasting actions of staurosporine, a protein kinase C inhibitor, on human neutrophils and primary mouse epidermal cells.
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发表时间：
1988-08
期刊：
影响因子：
11.2
通讯作者：
T. Sako;A. Tauber;A. Jeng;S. Yuspa;P. Blumberg
中科院分区：
文献类型：
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作者：
T. Sako;A. Tauber;A. Jeng;S. Yuspa;P. Blumberg
Staurosporine，最近描述的微生物生物碱，是唯一有效的蛋白激酶C在体外的抑制剂，是在nM浓度，而不是microM浓度的典型的其他抑制剂类的活性。然而，与这些其他抑制剂一样，星形孢菌素在不同蛋白激酶中仅表现出有限的选择性。我们在这里报告，在完整的人类中性粒细胞，nM浓度的星形孢菌素阻断佛波酯肿瘤促进剂的作用。另一方面，在小鼠原代表皮细胞中，星形孢菌素未能阻断佛波醇12，13-二丁酸酯对表皮生长因子结合以及对鸟氨酸脱羧酶和表皮转氨酶的诱导的影响。出乎意料的是，星形孢菌素诱导角质形成细胞的形态学变化为类似于佛波醇酯诱导的树突状。它还诱导表皮转氨酶和皮质包膜的产生，这是表皮细胞分化途径的标志物。我们得出结论，星形孢菌素作为蛋白激酶C抑制剂在完整细胞中的有效性可能显着依赖于细胞系统。星形孢菌素的其他作用可能占主导地位，并且在角质形成细胞中，其活性提示肿瘤促进剂而不是肿瘤促进的抑制剂。
Staurosporine, a recently described microbial alkaloid, is uniquely potent as an inhibitor of protein kinase C in vitro, being active at nM concentrations rather than the microM concentrations typical of other inhibitor classes. Like these other inhibitors, however, staurosporine exhibits only limited selectivity among different protein kinases. We report here that, in intact human neutrophils, nM concentrations of staurosporine blocked the action of the phorbol ester tumor promoters. In mouse primary epidermal cells, on the other hand, staurosporine failed to block the effects of phorbol 12,13-dibutyrate on epidermal growth factor binding and on induction of ornithine decarboxylase and epidermal transglutaminase. Unexpectedly, staurosporine induced morphological changes in keratinocytes to a dendritic shape resembling that induced by the phorbol esters. It also induced epidermal transglutaminase and cornified envelope production, markers of the differentiative pathway in the epidermal cells. We conclude that the effectiveness of staurosporine as a protein kinase C inhibitor in intact cells may depend markedly on the cell system. Other actions of staurosporine may predominate, and, in keratinocytes, its activity is suggestive of a tumor promoter rather than of an inhibitor of tumor promotion.