myosinelightchainkinase

Myosin light-chain kinase, often abbreviated MLCK, is a calcium/calmodulin-dependent serine/threonine kinase that phosphorylates the regulatory light chain of myosin II (RLC or MLC). Phosphorylation of MLC promotes myosin II-actin interactions and cross-bridge cycling, enabling contractile activity in muscle and non-muscle cells. The term myosinelightchainkinase appears to be a concatenated variant of this enzyme’s name.

In humans and other vertebrates, MLCK is encoded by the MYLK gene and exists as multiple isoforms produced by alternative splicing. Major isoforms include smooth muscle MLCK (smMLCK) and non-muscle MLCK (nmMLCK), as well as a skeletal muscle–specific form. Telokin (also known as MLCK-related protein) can be produced from alternative transcripts within the same gene region and has distinct regulatory effects on contraction. These isoforms differ in tissue distribution and regulatory regions, allowing MLCK activity to modulate contraction in smooth muscle, skeletal muscle, and a variety of non-muscle cells such as endothelial and epithelial cells.

Regulation occurs primarily through calcium signaling: increased intracellular Ca2+ binds calmodulin, forming a Ca2+-calmodulin complex that activates MLCK. MLCP (myosin light-chain phosphatase) counteracts MLCK by dephosphorylating MLC, providing a key mechanism for smooth muscle tone and cytoskeletal dynamics. MLCK activity influences processes beyond contraction, including cell migration, cytokinesis, and maintenance of cell shape.

Clinical and physiological relevance includes regulation of vascular tone, airway reactivity, and tissue remodeling. Dysregulation of MLCK signaling has been linked to hypertension, asthma, and certain cancer cell behaviors, making MLCK a focus of basic research and potential therapeutic exploration.