Human Lim Domain Kinase 1, LIMK1 ELI

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 (PubMed: 10436159, PubMed: 11832213, PubMed: 12807904, PubMed: 15660133, PubMed: 16230460, PubMed: 18028908, PubMed: 22328514, PubMed: 23633677).

Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop (PubMed: 10436159).

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 (PubMed: 11832213, PubMed: 15660133, PubMed: 16230460, PubMed: 23633677).

In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation (PubMed: 11832213, PubMed: 15660133, PubMed: 16230460, PubMed: 23633677).

Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly (PubMed: 18028908).

Stimulates axonal outgrowth and may be involved in brain development (PubMed: 18028908).

[Isoform 3]: Has a dominant negative effect on actin cytoskeletal changes.

Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1).