Inhibitory effect of phosphorylated myosin light chain kinase on the ATP-dependent actin-myosin interaction.
Myosin light chain kinase (MLCK) phosphorylates the regulatory light chain of myosin in the presence of Ca(2+) and calmodulin (Ca(2+)-CaM) so that myosin can interact with actin filaments. MLCK has another activity that is not attributable to this kinase activity, i.e., it inhibits the ATP-dependent movement of actin filaments on a myosin-coated glass surface. MLCK itself can be phosphorylated at site A and site B with a few kinases. The phosphorylation at site A reduces kinase activity. However, we have no knowledge as to how phosphorylation of MLCK affects the inhibitory activity of MLCK. When MLCK was phosphorylated at site B, it exerted an inhibitory effect on the movement in much lower concentrations. When Ca(2+)-CaM or ML-9 was present, the inhibition was reduced. The reduction was less when the movement was arrested by the MLCK phosphorylated at site B. This observation was explained by the increase in the affinity of MLCK to myosin upon the phosphorylation at site B.
Department of Pharmacology, Gunma University School of Medicine, Maebashi, Gunma, 371-8511, Japan. ksamizo@akagi.sb.gunma-u.ac.jp
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D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology; D002645:Chickens; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects
D000199:Actins; D001381:Azepines; D002147:Calmodulin; C056218:ML 9; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D009219:Myosin-Light-Chain Kinase; D009218:Myosins; D002118:Calcium