Regulation of Ca2+/calmodulin-dependent protein kinase IV (CaM-kinase IV) by changing its susceptibility to phosphorylation by CaM-kinase kinases

Calmodulin-dependent protein kinase IV (CaM-kinase IV) is markedly activated on the phosphorylation of Thr(196) by an upstream protein kinase, CaM-kinase kinase. The phosphorylation of CaM-kinase IV by CaM-kinase kinase is strongly suppressed on incubation with calmodulin in the presence of Ca2+, which results in a decrease in the enzyme activity, and completely restored on subsequent incubation with Mg2+ in the absence of Ca2+, which results in an increase in the activity. That a downstream protein kinase regulates its activity through reversible changes in its susceptibility to phosphorylation by an upstream protein kinase is a new regulatory mechanism.