PHOSPHORYLATION OF MYOSIN LIGHT-CHAIN KINASE - A CELLULAR MECHANISM FOR CA2+ DESENSITIZATION

Phosphorylation of the regulatory light chain of myosin by the Ca2+/ca lmodulin-dependent myosin light chain kinase plays an important role i n smooth muscle contraction, nonmuscle cell shape changes, platelet co ntraction, secretion, and other cellular processes. Smooth muscle myos in light chain kinase is also phosphorylated, and recent results from experiments designed to satisfy the criteria of Krebs and Beavo for es tablishing the physiological significance of enzyme phosphorylation ha ve provided insights into the cellular regulation and function of this phosphorylation in smooth muscle. The multifunctional Ca2+/calmodulin -dependent protein kinase II phosphorylates myosin light chain kinase at a regulatory site near the calmodulin-binding domain. This phosphor ylation increases the concentration of Ca2+/calmodulin required for ac tivation and hence increases the Ca2+ concentrations required for myos in light chain kinase activity in cells. However, the concentration of cytosolic Ca2+ required to effect myosin light chain kinase phosphory lation is greater than that required for myosin light chain phosphoryl ation. Phosphorylation of myosin light chain kinase is only one of a n umber of mechanisms used by the cell to down regulate the Ca2+ signal in smooth muscle. Since both smooth and nonmuscle cells express the sa me form of myosin light chain kinase, this phosphorylation may play a regulatory role in cellular processes that are dependent on myosin lig ht chain phosphorylation. (Mel Cell Biochem 127/128: 229-237, 1993)