Myosin light chain kinase 4 (MYLK4)

Myosin light chain kinase 4 (MYLK4), also known as SgK085, is a member of the calcium/calmodulin-dependent protein kinase family that specifically phosphorylates the regulatory light chain of myosin II [UniProt, Wikipedia, NCBI]. While its physiological role was initially less characterized than other family members, recent studies have identified MYLK4 as a significant player in oncogenesis and ocular physiology [PubMed, IOVS]. In cancers such as osteosarcoma and colorectal cancer, MYLK4 is frequently overexpressed and promotes tumor growth and metastasis by activating the EGFR signaling pathway or modulating lipid metabolism to prevent ferroptosis [PubMed, PMC]. Additionally, MYLK4 has emerged as a therapeutic target for glaucoma, where its inhibition, often in combination with Rho-associated kinase (ROCK) inhibition, effectively lowers intraocular pressure [BioWorld, IOVS]. Pharmacological targeting of MYLK4 is currently being explored through small-molecule inhibitors, with a focus on achieving selectivity to avoid off-target effects on other essential myosin light chain kinases [BioWorld, PubMed]. Its role in skeletal muscle strength through the androgen receptor axis further highlights its diverse biological impact [ResearchGate].

Other names

MYLK4SgK085SGK085Sugen kinase 85CaMLCK likeMyosin light chain kinase family member 4Uncharacterized serine/threonine-protein kinase SgK085

Small-molecule inhibition of MYLK4 kinase activity prevents the phosphorylation of the myosin regulatory light chain (RLC/LC20) and other substrates, thereby disrupting actomyosin-mediated processes such as cell migration, tumor growth, and aqueous humor outflow resistance.