Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes

被引:587
作者
Gschwendt, M
Dieterich, S
Rennecke, J
Kittstein, W
Mueller, HJ
Johannes, FJ
机构
[1] UNIV STUTTGART, INST CELL BIOL & IMMUNOL, D-70569 STUTTGART, GERMANY
[2] GERMAN CANC RES CTR, D-6900 HEIDELBERG, GERMANY
关键词
protein kinase C mu; protein kinase C isoenzyme; protein kinase C inhibitor; staurosporine; autophosphorylation;
D O I
10.1016/0014-5793(96)00785-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:77 / 80
页数:4
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