EFFECTS OF CATIONIC POLYPEPTIDES ON THE ACTIVITY, SUBSTRATE INTERACTION, AND AUTOPHOSPHORYLATION OF CASEIN KINASE-II - A STUDY WITH CALMODULIN

The effects of basic polypeptides on the ability of casein kinase II to phosphorylate an exogenous substrate (calmodulin) are correlated with steady-state autophosphorylation of the α- and β-subunits of casein kinase II. Polylysine and polyarginine increase autophosphorylation of the α-subunit with a concomitant decrease in β-subunit phosphorylation, while enhancing casein kinase II-stimulated phosphorylation of calmodulin over 100-fold. The highly basic carboxyl terminal segment of the endogenous p21c-Ki-ras has similar effects on the phosphorylation of calmodulin and the α- and β-subunits of casein kinase II. Altering the concentration of cationic polypeptides produces a biphasic effect on the phosphorylation of both calmodulin and the α-subunit, which correlate positively with each other but do not correlate with β-subunit phosphorylation. When the KCl concentration is changed, casein kinase II activity correlates positively only with α-subunit phosphorylation. In contrast, the biphasic response of calmodulin phosphorylation by casein kinase II at different Ca2+ concentrations correlates positively with both α- and β-subunit phosphorylation. Therefore, in the presence of basic protein activators, the rate of phosphorylation of a substrate, calmodulin, correlates with steady-state phosphorylation of the α-subunit, but not with the β-subunit under all conditions tested. Endogenous cationic factors may modulate the in vivo activity of casein kinase II and alter the interaction of the enzyme with specific intracellular substrates. © 1992.