Regulation of myosin light-chain phosphorylation and its roles in cardiovascular physiology and pathophysiology

The regulation of muscle contraction is a critical function in the cardiovascular system, and abnormalities may be life-threatening or cause illness. The common basic mechanism in muscle contraction is the interaction between the protein filaments myosin and actin. Although this interaction is primarily regulated by intracellular Ca2+, the primary targets and intracellular signaling pathways differ in vascular smooth muscle and cardiac muscle. Phosphorylation of the myosin regulatory light chain (RLC) is a primary molecular switch for smooth muscle contraction. The equilibrium between phosphorylated and unphosphorylated RLC is dynamically achieved through two enzymes, myosin light chain kinase, a Ca2+-dependent enzyme, and myosin phosphatase, which modifies the Ca2+ sensitivity of contractions. In cardiac muscle, the primary target protein for Ca2+ is troponin C on thin filaments; however, RLC phosphorylation also plays a modulatory role in contraction. This review summarizes recent advances in our understanding of the regulation, physiological function, and pathophysiological involvement of RLC phosphorylation in smooth and cardiac muscles.