Environmental pollutant Cd2+ biphasically and differentially regulates myosin light chain kinase and phospholipid/Ca2+‐dependent protein kinase

Cd2+ was found to mimic effectively, potentiate and antagonize the stimulatory action of Ca2+ on myosin light chain kinase (MLCK) and phospholipid‐sensitive Ca2+‐dependent protein kinase (PL‐Ca‐PK, or protein kinase C). PL‐Ca‐PK, however, was slightly less sensitive to Cd2+ regulation than was MLCK. Cd2+ also biphasically regulates (i.e., stimulation followed by inhibition) phosphorylation, in the homogenates of the rat caudal artery, of myosin light chain and other endogenous proteins catalyzed by MLCK and PL‐Ca‐PK. The activation by Cd2+ of MLCK was inhibited by anticalmodulins (e.g., R‐24571), whereas the inhibition by a higher Cd2+ concentration of MLCK and PL‐Ca‐PK was reversed by thiol agents (e.g., cysteine). The present findings may provide one mechanism underlying the vascular toxicity of Cd2+, a major environmental pollutant.