Use of a drug-resistant mutant of stress-activated protein kinase 2a/p38 to validate the in vivo specificity of SE 203580
Use of a drug-resistant mutant of stress-activated protein kinase 2a/p38 to validate the in vivo specificity of SE 203580
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DOI：
10.1016/s0014-5793(99)00552-9
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发表时间：
1999-05-21
期刊：
影响因子：
3.5
通讯作者：
Cohen, P
中科院分区：
文献类型：
--
作者：
Eyers, PA;van den Ijssel, P;Cohen, P
应激激活蛋白激酶2a，也称为p38，被SE 203580抑制，并且该药物已被广泛用于使该酶参与许多生理过程的调节。在这里，我介绍了一种新的方法的一般应用，它可以用来确定是否SE 203580的影响是通过抑制应激活化蛋白激酶2a/p38介导的，或者他们是否从“非特异性”的影响。四个事件被认为是发生在激活应激活化蛋白激酶2a/p38已明确确立。这些分别是促分裂原活化蛋白激酶活化蛋白激酶-2和促分裂原和应激活化蛋白激酶-1的活化以及它们的假定底物热休克蛋白27和转录因子环AMP反应元件结合蛋白的磷酸化。相比之下，SB 203580诱导的c-Raf活化不依赖于应激活化蛋白激酶2a/p38抑制。(C)1999年欧洲生物化学学会联合会。
Stress-activated protein kinase 2a, also called p38, is inhibited by SE 203580 and this drug has been used widely to implicate this enzyme in the regulation of many physiological processes. Here, me introduce a novel method of general application, which can be used to establish whether the effects of SE 203580 are mediated via inhibition of stress-activated protein kinase 2a/p38 or whether they result from 'non-specific' effects. Four events thought to occur upon activation of stress-activated protein kinase 2a/p38 have been established unequivocally. These are the activation of mitogen-activated protein kinase-activated protein kinase-2 and mitogen- and stress-activated protein kinase-1 and the phosphorylation of their presumed substrates, heat shock protein 27 and the transcription factor cyclic AMP response element binding protein, respectively. In contrast, the SB 203580-induced activation of c-Raf is independent of stress-activated protein kinase 2a/p38 inhibition. (C) 1999 Federation of European Biochemical Societies.