Effect of the rare earth elements on phosphatase activity of calcineurin

Abstract

The rare earth elements are a group of 17 elements including scandium (Sc), yttrium (Y), and lanthanoids from lanthanum (La) to lutetium (Lu). These elements are used in industrial materials such as capacitors and lenses and also play active physiological and biological roles in the human body. On the other hand, calcineurin (CN), also known as protein phosphatase 2B (PP2B), is a Ca²⁺/calmodulin-dependent protein, and Ser/Thr phosphatase is recognized as a therapeutic target for the immunosuppressive drugs cyclosporin A and FK506. In this study, we examined the effects of rare earth elements, including lanthanum ions (La³⁺), in vitro on the phosphatase activity of CN using recombinant human calcineurin (rhCN) from Escherichia coli and RII phosphopeptide as a substrate. We found that rhCN activity was inhibited by rare earth elements including La³⁺. To further examine the effect of La³⁺ inhibition on rhCN activity, we performed kinetic analysis. According to a Lineweaver–Burk plot, the phosphatase activity of rhCN showed mixed type inhibition. The inhibition constants were 7.0 μM for rhCN and 10.2 μM for rhCN-R II phosphopeptide complex.