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

Various inhibitors were tested for their potential to suppress the kinase activity of protein kinase C μ (PKCμ) in vitro and in vivo. Among the staurosporine‐derived, rather selective PKC inhibitors the indolocarbazole Gö 6976 previously shown to inhibit preferentially cPKC isotypes proved to be a potent inhibitor of PKCμ with an IC 5 of 20 nM, whereas the bisindolymaleimide Gö 6983 was extremely ineffective in suppressing PKCμ kinase activity with a thousand‐fold higher ICm of 20 μM. Other strong inhibitors of PKCμ were the rather unspecific inhibitors staurosporine and K252a. Contrary to the poor inhibition of PKCμ by Gö 6983, this compound was found to suppress in vitro kinase activity of PKC isoenzymes from all three subgroups very effectively with IC 50 values from 7 to 60 nM. Thus, Gö 6983 was able to differentiate between PKCμ and other PKC isoenzymes being useful for selective determination of PKCμ kinase activity in the presence of other PKC isoenzymes.