LIM domain kinase (LIMK) (LIMK)

LIM domain kinase (LIMK) is a family of serine/threonine kinases, including LIMK1 and LIMK2, that serve as critical regulators of actin cytoskeleton dynamics (UniProt P53667, P53671). These enzymes function by phosphorylating and inactivating cofilin, an actin-depolymerizing factor, thereby promoting the stabilization of actin filaments (PubMed: 22924358). This pathway is downstream of Rho-family GTPases, such as Rho, Rac, and Cdc42, which activate LIMK via ROCK or PAK (PubMed: 11259372). In clinical contexts, LIMK is often overexpressed in various cancers, where it facilitates cell migration, invasion, and metastasis (PubMed: 25605116). Additionally, LIMK1 is essential for proper neuronal development and synaptic plasticity; its haploinsufficiency is a hallmark of Williams syndrome, contributing to specific cognitive impairments (PubMed: 8673106). Pharmacological inhibition of LIMK is being explored as a strategy to arrest cancer progression and treat conditions like glaucoma by modulating cellular contractility and motility (PubMed: 22924358).

Other names

LIMK1LIMK2LIM domain-containing protein kinaseCofilin kinase

Inhibition of LIM domain kinase prevents the phosphorylation of cofilin, thereby maintaining cofilin in its active state to promote actin filament depolymerization and severing, which disrupts cell migration and cytoskeletal remodeling (PubMed: 22924358).