LIM domain kinase 1

Definition:

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).

References:

[1]. D C Edwards, et al. Structural features of LIM kinase that control effects on the actin cytoskeleton. J Biol Chem. 1999 Apr 16;274(16):11352-61. [Content Brief]

[2]. M Maekawa, et al. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science. 1999 Aug 6;285(5429):895-8. [Content Brief]

[3]. Ryusuke Niwa, et al. Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell. 2002 Jan 25;108(2):233-46. [Content Brief]

[4]. Juliana Soosairajah, et al. Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005 Feb 9;24(3):473-86. [Content Brief]

[5]. Karla Acevedo, et al. The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to assemble microtubules. Exp Cell Res. 2007 Dec 10;313(20):4091-106. [Content Brief]

[6]. Noriko Kaji, et al. Cell cycle-associated changes in Slingshot phosphatase activity and roles in cytokinesis in animal cells. J Biol Chem. 2003 Aug 29;278(35):33450-5. [Content Brief]

[7]. Yi-Wen Heng, et al. TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation. J Cell Sci. 2012 Mar 15;125(Pt 6):1579-90. [Content Brief]

[8]. Michiru Nishita, et al. Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration. J Cell Biol. 2005 Oct 24;171(2):349-59. [Content Brief]

[9]. Elena M Borroni, et al. β-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6. Sci Signal. 2013 Apr 30;6(273):ra30.1-11, S1-3. [Content Brief]

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