Calcium/calmodulin-dependent protein kinase II (CaMPK-II) is a key regulatory enzyme in living cells. Modulation of its activity, therefore, could have a major impact on many cellular processes. We found that Zn²⁺ has multiple functional effects on CaMPK-II. Zn²⁺ generated a Ca²⁺/CaM-independent activity that correlated with the autophosphorylation of Thr²⁸⁶, inhibited Ca²⁺/CaM binding that correlated with the autophosphorylation of Thr³⁰⁶, and inhibited CaMPK-II activity at high concentrations that correlated with the autophosphorylation of Ser²⁷⁹. The relative level of autophosphorylation of these three sites was dependent on the concentration of zinc used. The autophosphorylation of at least these three sites, together with Zn²⁺ binding, generated an increased mobility form of CaMPK-II on sodium dodecyl sulfate gels. Overall, autophosphorylation induced by Zn²⁺ converts CaMPK-II into a different form than the binding of Ca2+/CaM. In certain nerve terminals, where Zn²⁺ has been shown to play a neuromodulatory role and is present in high concentrations, Zn²⁺ may turn CaMPK-II into a form that would be unable to respond to calcium signals.
Journal of Neurochemistry Vol. 75 , Issue 2, p. 594-605