Lim Kinases

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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. Upstream, LIMK1 is regulated by Pak1 (Edwards et al, 1999), and LIMK2 by the Rho-dependent kinase ROCK (Sumi et al, 2001). Lim Kinases are activated by PAK (p21-activated kinase).

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. NIH

[edit] References

  1. Aizawa, H., Wakatsuki, S., Ishii, A., Moriyama, K., Sasaki, Y., Ohashi, K., Sekine-Aizawa, Y., Sehara-Fujisawa, A., Mizuno, K., Goshima, Y. & Yahara, I. (2001) Phosphorylation of cofilin by LIM kinase is necessary for semaphorin 3A-induced growth cone collapse., Nature Neuroscience. 4, 367-373.
  2. Amano, T., Tanabe, K., Eto, T., Narumiya, S. & Mizuno, K. (2001) LIM-kinase 2 induces formation of stress fibres, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase-catalysed phopshorylation at threonine-505., Biochem. J. 354, 149-159.
  3. Edwards, D.C., Sanders, L.C., Bokoch, G.M. & Gill, G.N. (1999) Nature Cell Biol. 1, 253-259.
  4. Sumi, T., Matsumoto, K. & Nakamura, T. (2001). "Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase." J.Biol.Chem. 276(1), 670-676.
  5. NIH LIMK1 LIM domain kinase 1 Homo sapiens
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