ACTIVATION OF Ca²⁺/CALMODULIN-DEPENDENT PROTEIN KINASE II BY AUTOPHORYLATION: SPECIFIED SUBSTRATES ENHANCE THE KINASE ACTIVITY

Abstract

The effects of autophosphorylation of brain Ca²⁺/calmodulin-dependent protein kinase II were investigated using several substrates. The autophosphorylation of the enzyme increased the Ca²⁺/calmodulin-independent activity with any of the substrates used. When myelin basic protein or calcineurin was used as substrate, the total kinase activity was prominently increased by autophosphorylation, suggesting that the enzyme is activated by autophosphorylation. Since this effect was not observed with chicken gizzard myosin light chain as substrate, the activation of the enzyme by autophosphorylation was dependent on substrate used. The addition of calmoduilin at higher concentrations inhibited the total activity of the autophosphorylated enzyme. The results suggest that the substrate specificity of the enzyme changes by autophosphorylation and that thereby the selectivity of the enzyme for substrates increases.