Survey of calcineurin activity towards nonprotein compounds and identification of phosphoenol pyruvate as a substrate.

Calcineurin, originally identified as a calmodulin-dependent phosphoprotein phosphatase (Stewart, A.A. et al. (1982) FEBS Lett. 137, 80-84) also uses p-nitrophenyl phosphate and phosphotyrosine as substrates (Pallen, C.J. and Wang, J.H. (1983) J. Biol. Chem. 258, 8550-8553). We have surveyed a wide range of nonprotein phosphocompounds and found that several synthetic aryl phosphocompounds serve as calcineurin substrates. Among more than 20 naturally occurring phosphocompounds tested, only phosphoenol pyruvate possesses significant calcineurin substrate activity. The phosphoenol pyruvate phosphatase activity is dependent on Ni2+ and Mn2+, is stimulated by calmodulin, and is inhibited by a monoclonal antibody to calcineurin, thus indicating that it is an intrinsic property of calcineurin. The results suggest that functional roles of calcineurin may include actions of the enzyme toward nonprotein phosphocompounds.