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 Km's obtained with Ca2+ and Ni2+ were 2.2 and 4.2 microM, and the kcat'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.
D000818:Animals; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D009532:Nickel / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity; D014364:Tryptophan
D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D002413:Cations, Divalent; D009532:Nickel; D014364:Tryptophan; D010749:Phosphoprotein Phosphatases