双吲哚马来酰亚胺（蛋白激酶C的选择性抑制剂）的同工酶特异性
Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C.
作者信息
Wilkinson S E, Parker P J, Nixon J S
机构信息
Research Centre, Roche Products Ltd., Welwyn Garden City, Herts, U.K.
出版信息
Biochem J. 1993 Sep 1;294 ( Pt 2)(Pt 2):335-7. doi: 10.1042/bj2940335.
Abstract
The protein kinase C (PKC) family of isoenzymes is believed to mediate a wide range of signal-transduction pathways in many different cell types. A series of bisindolylmaleimides have been evaluated as inhibitors of members of the conventional PKC family (PKCs-alpha, -beta, -gamma) and of a representative of the new, Ca(2+)-independent, PKC family, PKC-epsilon. In contrast with the indolocarbazole staurosporine, all the bisindolylmaleimides investigated showed slight selectivity for PKC-alpha over the other isoenzymes examined. In addition, bisindolylmaleimides bearing a conformationally restricted side-chain were less active as inhibitors of PKC-epsilon. Most noticeable of these was Ro 32-0432, which showed a 10-fold selectivity for PKC-alpha and a 4-fold selectivity for PKC-beta I over PKC-epsilon.
摘要
蛋白激酶C（PKC）同工酶家族被认为在许多不同细胞类型中介导广泛的信号转导途径。一系列双吲哚马来酰胺已被评估为传统PKC家族成员（PKC-α、-β、-γ）以及新型、不依赖Ca²⁺的PKC家族代表PKC-ε的抑制剂。与吲哚咔唑星形孢菌素不同，所有研究的双吲哚马来酰胺对PKC-α的选择性略高于其他检测的同工酶。此外，带有构象受限侧链的双吲哚马来酰胺作为PKC-ε的抑制剂活性较低。其中最显著的是Ro 32-0432，它对PKC-α的选择性为10倍，对PKC-βI的选择性比对PKC-ε高4倍。
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本文引用的文献
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