Requirement of brain extract for the activity of brain calmodulin-dependent protein kinase IV expressed in Escherichia coli.

Calmodulin-dependent protein kinase IV (CaM-kinase IV) is a Ca(2+)-responsive multifunctional protein kinase which occurs abundantly in the brain. When cDNA for rat brain CaM-kinase IV was expressed in Escherichia coli, the enzyme was produced in a good yield, but it did not show significant activity. The inactive recombinant CaM-kinase IV was phosphorylated and became highly active on incubation with a rat brain extract in the presence of both Ca2+/calmodulin and ATP/Mg2+. The recombinant CaM-kinase IV-activating activity in brain was one to two orders of magnitude higher than that in the other tissues examined. These observations suggest that CaM-kinase IV may undergo a posttranslational modification, probably Ca2+/calmodulin-dependent phosphorylation by CaM-kinase IV kinase, before exhibiting activity in the central nervous system.