Identification of pharmacological inhibitors of the MEK5/ERK5 pathway
Identification of pharmacological inhibitors of the MEK5/ERK5 pathway
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DOI：
10.1016/j.bbrc.2008.09.087
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发表时间：
2008-12-05
影响因子：
3.1
通讯作者：
Snow, Roger J.
中科院分区：
文献类型：
--
作者：
Tatake, Revati J.;O'Neill, Margaret M.;Snow, Roger J.
我们发现了两种新的MEK5抑制剂BIX02188和BIX02189，它们抑制纯化的MEK5酶的催化功能。在山梨醇刺激的HeLa细胞中，MEK5抑制剂阻断ERK5的磷酸化，而不影响ERK1/2的磷酸化。在细胞反报告蛋白检测系统中，这些化合物还抑制MEF2C的转录激活，MEF2C是MEK5/ERK5信号级联的下游底物。这些抑制剂提供了新的药理学工具，以更好地表征MEK5/ERK5通路在各种生物系统中的作用。(C) 2008爱思唯尔公司版权所有。
We have identified two novel MEK5 inhibitors, BIX02188 and BIX02189, which inhibited catalytic function of purified, MEK5 enzyme. The MEK5 inhibitors blocked phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells. The compounds also inhibited transcriptional activation of MEF2C, a downstream substrate of the MEK5/ERK5 signaling cascade, in a cellular trans-reporter assay system. These inhibitors offer novel pharmacological tools to better characterize the role of the MEK5/ERK5 pathway in various biological systems. (C) 2008 Elsevier Inc. All rights reserved.