Regulation of contractile proteins by reversible phosphorylation of myosin and myosin kinase.

In vitro experiments support the ideal that the actin-activated MgATPase activity of smooth muscle myosin and myosin from nonmuscle cells is regulated by the phosphorylation of the 20,000 dalton light chain of myosin. Experiments with intact smooth muscles support this mechanism but also raise the possibility that tension may be maintained in the presence of partial dephosphorylation (12). The possibility that smooth muscle contraction may also be modulated by additional regulatory systems (13,29) is to be expected based on experience with other types of muscle. The enzyme myosin light chain kinase catalyzes the phosphorylation of the 20,000 dalton light chain of myosin. This enzyme requires Ca2+-calmodulin for activity. The activity of myosin kinases that have been isolated from avian smooth muscle cells (8) or human platelets (16) can be decreased by phosphorylation. This phosphorylation is catalyzed by cAMP-dependent protein kinase and decreases myosin kinase activity by interfering with the binding of Ca2+-calmodulin. A number of different phosphatases have been purified from smooth muscle (22). These phosphatases play an important role in determining the state of phosphorylation of myosin and myosin kinase. Two areas of particular interest at present are the regulation of phosphatase activity and the physiological significance of myosin kinase phosphorylation.