Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase
Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase
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DOI：
10.1016/j.chembiol.2004.11.009
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发表时间：
2005-01-01
影响因子：
--
通讯作者：
Rosenblum, JS
中科院分区：
文献类型：
--
作者：
Liu, YS;Shreder, KR;Rosenblum, JS
Polo样激酶（PLK）在有丝分裂过程中起关键作用。在这里，我们报告，渥曼青霉素，这是以前被认为是一个高度选择性的磷酸肌醇（PI）3-激酶抑制剂，是一种有效的哺乳动物PLK 1抑制剂。通过四甲基罗丹明-渥曼青霉素缀合物（AX7503）能够观察渥曼青霉素-PLK 1相互作用，所述缀合物允许快速检测PLK 1活性和在复杂蛋白质组中的表达。重要的是，我们发现渥曼青霉素在体外激酶试验中抑制PLK 1活性，IC 50为24 nM，并且与完整细胞孵育时。总之，我们的结果表明，在通常用于抑制PI 3-激酶的渥曼青霉素浓度下，PLK 1也被显著抑制。
Polo-like kinases (PLKs) play critical roles throughout mitosis. Here, we report that wortmannin, which was previously thought to be a highly selective inhibitor of phosphoinositide (PI) 3-kinases, is a potent inhibitor of mammalian PLK1. Observation of the wortmannin-PLK1 interaction was enabled by a tetra-methylrhodamine-wortmannin conjugate (AX7503) that permits rapid detection of PLK1 activity and expression in complex proteomes. Importantly, we show that wortmannin inhibits PLK1 activity in an in vitro kinase assay with an IC50 of 24 nM and when incubated with intact cells. Taken together, our results indicate that, at the concentrations of wortmannin commonly used to inhibit PI 3-kinases, PLK1 is also significantly inhibited.