Characterization of phosphotyrosyl-protein phosphatase activity associated with calcineurin

Calcineurin purified from bovine brain is shown to possess phosphotyrosyl-protein phosphatase activity towards proteins phosphorylated by the epidermal growth factor receptor/kinase. The phosphatase activity is augmented by Ca²⁺/calmodulin or divalent cation (Ni²⁺ > Mn²⁺ > Mg²⁺ > Co²⁺). In the simultaneous presence of all three effectors the enzymatic activity is synergistically increased. Ca²⁺/calmodulin activates the Mg²⁺-supported activity by decreasing the K_m value for phosphotyrosyl-casein from 2.2 to 0.6 μM, and increasing the V_max from 0.4 to 4.6 nmol/min/mg. These results represent the first demonstration that calcineurin can dephosphorylate phosphotyrosyl-proteins and suggest a novel mechanism of activation of this enzyme.