Regulation of myosin phosphorylation

Abstract

Myosin light chain kinase catalyzes the phosphorylation of a particular light chain subunit of myosin. Myosin light chain kinases from different types of mammalian muscles demonstrate different enzymatic and physical properties which suggest that there may be isozymic forms. The enzymes from mammalian skeletal, cardiac and smooth muscles are dependent upon both Ca 2+ and calmodulin for activity. From a kinetic analysis of the activation process, the following sequence of reactions is proposed: ▪ This hypothesis suggests that all 4 divalent metal-binding sites in calmodulin must be filled with Ca 2+ before myosin light chain kinase is activated by calmoldulin. Furthermore, activation results from binding of one calmoldulin to one catalytic subunit of myosin light chain kinase. In addition to the kinetics of Ca 2+ release and resequestration, some of the important determinants governing the rate of phosphorylation of myosin in living muscles include the concentration and catalytic activity of myosin light chain kinase, calmodulin concentration and the amount of myosin light chain phosphatase activity. The rates of phosphorylation and dephosphorylation of myosin light chain in cardiac and skeletal muscles are much slower than the rates of contraction and relaxation. Hence it is not likely that myosin light chain would be phosphorylated and then dephosphorylated during a single contraction cycle. However, the slow rate of contraction and relaxation in smooth muscle could be closely linked to phosphorylation and dephosphorylation, respectively.