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7802607 
Journal Article 
Regulation of calcineurin by metal ions. Mechanism of activation by Ni2+ and an enhanced response to Ca2+/calmodulin 
Pallen, CJ; Wang, JH 
1984 
Yes 
Journal of Biological Chemistry
ISSN: 0021-9258
EISSN: 1083-351X 
259 
10 
6134-6141 
English 
6327669 
Calcineurin possesses phosphatase activity towards both protein (Stewart, A.A., Ingebritsen , T.S., Manalan , A., Klee , C.B., and Cohen, P. (1982) FEBS Lett. 137, 80-84) and nonprotein substrates ( Pallen , C.J., and Wang, J.H. (1983) J. Biol. Chem. 258, 8550-8553). These phosphatase activities are divalent cation-dependent and stimulated by calmodulin. We have utilized the nonprotein chromogenic substrate p-nitrophenyl phosphate to investigate the effects of several divalent metal ions on calcineurin activity and have found that Ni2+ is the best activator of calcineurin both in the presence and absence of calmodulin. A slightly less potent activator is Mn2+. Although the mechanisms and extents of activation stimulated by these two metal ions are different, we present evidence to suggest a competition for binding to the enzyme. Pretreatment of calcineurin with either of these two metal ions enhances the activation of calcineurin by Ca2+/calmodulin and may be a physiological mechanism by which calcineurin activity is regulated by Ca2+. 
Animals; Brain/metabolism; Calcium/metabolism; Calmodulin/metabolism; Calmodulin-Binding Proteins; Cations, Divalent; Edetic Acid/pharmacology; Kinetics; Manganese/pharmacology; Nickel/pharmacology; Phosphoprotein Phosphatases/metabolism