功能 |
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).
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總結(jié) |
LIM kinases (LIMK1 and LIMK2) are serine/threnine kinases that have two zinc finger motifs, known as LIM motifs in their N-terminal regulatory domain. LIM kinases are involved in actin cytoskeleton regulation thro μgh Rho-family GTPases and downstream kinases PAKs and ROCK. PAK1 and ROCK phosphorylate LIMK1 and LIMK2, which increases the activity of the kinases. Activated LIM kinases inhibit the actin depolymerization activity of cofilin by phosphorylation at the N-terminus of Cofilin.
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