| Post Translational Modifications | Autophosphorylated. Phosphorylated on Thr-508 by ROCK1 and PAK1, resulting in activation. Phosphorylated by PAK4 which increases the ability of LIMK1 to phosphorylate cofilin. Phosphorylated at Ser-323 by MAPKAPK2 during activation of VEGFA-induced signaling, which results in activation of LIMK1 and promotion of actin reorganization, cell migration, and tubule formation of endothelial cells. Dephosphorylated and inactivated by SSH1. Phosphorylated by CDC42BP. Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF6 leads to proteasomal degradation through the 26S proteasome, modulating LIMK1 levels in the growth cone and its effect on axonal outgrowth. Also polyubiquitinated by RLIM. |
| Function | Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop. LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton. In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation. Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly. Stimulates axonal outgrowth and may be involved in brain development. Isoform 3: Has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1). |
| Protein Name | Lim Domain Kinase 1Limk-1 |
| Database Links | Reactome: R-HSA-2029482Reactome: R-HSA-3928662Reactome: R-HSA-399954Reactome: R-HSA-416572Reactome: R-HSA-5627117Reactome: R-HSA-5627123 |
| Cellular Localisation | CytoplasmNucleusCytoskeletonCell ProjectionLamellipodiumPredominantly Found In The CytoplasmLocalizes In The Lamellipodium In A Cdc42bpaCdc42bpb And Fam89b/Lrap25-Dependent Manner |
| Alternative Protein Names | Lim Domain Kinase 1 proteinLimk-1 proteinLIMK1 proteinLIMK protein |
Information sourced from Uniprot.org
