Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes
Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes
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DOI：
10.1016/0014-5793(96)00785-5
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发表时间：
1996-08-26
期刊：
影响因子：
3.5
通讯作者：
Johannes, FJ
中科院分区：
文献类型：
--
作者：
Gschwendt, M;Dieterich, S;Johannes, FJ
测试了各种抑制剂在体外和体内抑制蛋白激酶C μ（PKC μ）的激酶活性的潜力。在staurosporine衍生的，而选择性的PKC抑制剂的吲哚咔唑Go 6976以前显示出优先抑制cPKC同种型被证明是一个有效的抑制剂的PKC μ的IC 50为20 nM，而双吲哚马来酰亚胺Go 6983是非常无效的抑制PKC μ激酶活性，具有千倍高的IC 50为20 μ M。PKC μ的其他强抑制剂是非特异性抑制剂staurosporine和K252a。与Go 6983对PKC μ的不良抑制相反，发现该化合物非常有效地抑制来自所有三个亚组的PKC同工酶的体外激酶活性，IC 50值为7至60 nM。因此，Go 6983能够区分PKC μ和其他PKC同工酶，可用于在其他PKC同工酶存在下选择性测定PKC μ激酶活性。
Various inhibitors were tested for their potential to suppress the kinase activity of protein kinase C mu (PKC mu) in vitro and in vivo. Among the staurosporine-derived, rather selective PKC inhibitors the indolocarbazole Go 6976 previously shown to inhibit preferentially cPKC isotypes proved to be a potent inhibitor of PKC mu with an IC50 of 20 nM, whereas the bisindolylmaleimide Go 6983 was extremely ineffective in suppressing PKC mu kinase activity with a thousand-fold higher IC50 of 20 mu M. Other strong inhibitors of PKC mu were the rather unspecific inhibitors staurosporine and K252a. Contrary to the poor inhibition of PKC mu by Go 6983, this compound was found to suppress in vitro kinase activity of PKC isoenzymes from all three subgroups very effectively with IC50 values from 7 to 60 nM. Thus, Go 6983 was able to differentiate between PKC mu and other PKC isoenzymes being useful for selective determination of PKC mu kinase activity in the presence of other PKC isoenzymes.