Lim Kinases

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).

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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

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