Activation of calcineurin by nickel ions

Calcineurin, a Ca²⁺- and calmodulin-dependent phosphoprotein phosphatase, was dramatically activated by Ni²⁺ ions. Activation by Ni²⁺ was independent of calmodulin and was not reversed by high concentrations of chelators. With histone H1 as substrate, the K_m's obtained with Ca²⁺ and Ni²⁺ were 2.2 and 4.2 μM, and the k_cat's were 0.5 and 24.3 min^?1, respectively. Similar to the Ca²⁺- and Mn²⁺- supported reactions, the presence of calmodulin caused a 20-fold activation of the Ni²⁺-activated calcineurin over the basal rate. Incubation of calcineurin with Ni²⁺ resulted in 30% quenching of its Trp-fluorescence. This effect also was independent of calmodulin and not reversed by chelators. The results suggest that the Ni²⁺ ions are tightly bound to calcineurin and the effects may be physiologically relevant.