Calcineurin is a calmodulin-dependent protein phosphatase

Calcineurin, one of the major calmodulin-binding proteins in the brain, dephosphorylates a phosphorylated protein termed inhibitor-1, a potent inhibitor of protein phosphatase 1. The phosphatase activity was Ca²⁺- and calmodulin-dependent and was reversed by EGTA or trifluoperazine, an antagonist of calmodulin. Using a radioimmunoassay of calcineurin and a phosphatase activity assay, we found that the two activities coincided in a sucrose density gradient and in a non-denaturing polyacrylamide gel. These results demonstrate that calcineurin is a calmodulin-dependent protein phosphatase.