Myosin light chain kinase (MYLK) (MYLK)

Myosin light chain kinase (MYLK) is a specialized calcium/calmodulin-dependent enzyme that serves as the primary regulator of contraction in vascular smooth muscle. Upon an increase in intracellular calcium, MYLK is activated by the calcium-calmodulin complex and subsequently phosphorylates the 20-kDa regulatory light chain of myosin (MLC20). This phosphorylation event is essential for the actin-activated ATPase activity of myosin, which drives the cross-bridge cycling necessary for muscle shortening and the maintenance of vascular tone. Dysregulation of MYLK activity is a significant factor in the pathophysiology of cardiovascular diseases such as hypertension and thoracic aortic aneurysms, as well as inflammatory conditions like asthma and acute respiratory distress syndrome (PMID: 2455124, UniProt: Q15746). The target name provided, "Vascular smooth muscle Ca²⁺-dependent ATPase / myofibrillar protein kinase," is a composite term often found in pharmacological literature describing the polypharmacology of drugs like bepridil. In this context, "myofibrillar protein kinase" refers specifically to MYLK, while "Ca²⁺-dependent ATPase" typically refers to the sarcoplasmic reticulum calcium ATPase (SERCA2), which is also inhibited by these agents (DrugBank: DB01244). Therapeutic targeting of MYLK aims to induce vasodilation and reduce peripheral resistance, although achieving tissue specificity remains a challenge to avoid systemic hypotension and adverse effects on vascular permeability.

Other names

Myofibrillar protein kinaseMLCKSmooth muscle myosin light chain kinaseMYLK1Calcium/calmodulin-dependent myosin light chain kinaseKRPTelokinMLCK108MLCK210

Inhibition of MYLK prevents the phosphorylation of the 20-kDa regulatory light chain of myosin (MLC20), which is required for actin-myosin cross-bridge formation and smooth muscle contraction.