LIM kinase-1 (LIMK1) and LIM kinase-2 (LIMK2) are actin-binding kinases that phosphorylate members of the ADF/cofilin family of actin binding and filament severing proteins. ADF/cofilin are the only substrates yet identified for the LIM kinases. LIM kinases directly phosphorylate and inactivate members of the cofilin family, resulting in stabilization of filamentous (F)-actin. Lim kinases are activated by signaling through small GTPases of the Rho family. Upstream, LIMK1 is regulated by Pak1,[1] and LIMK2 by the Rho-dependent kinase ROCK.[2] Lim Kinases are activated by PAK (p21-activated kinase). Recent work indicates that LIMK activity is also modulated by HIV-1 viral proteins.

There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein–protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. LIMK1 is likely to be a component of an intracellular signaling pathway and may be involved in brain development. LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome.[3]


  1. ^ Edwards, D.C., Sanders, L.C., Bokoch, G.M. & Gill, G.N. (1999) Nature Cell Biol. 1, 253–259.
  2. ^ Sumi, T., Matsumoto, K. & Nakamura, T. (2001). "Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK,
  3. ^ NIH