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.
D000818:Animals; D001158:Arteries / Q000201:enzymology; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity; D002417:Cattle; D003545:Cysteine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D009219:Myosin-Light-Chain Kinase; D010766:Phosphorylation; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D002104:Cadmium; D011494:Protein Kinases; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D003545:Cysteine