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Gene Review

LIMK1  -  LIM domain kinase 1

Homo sapiens

Synonyms: LIMK, LIMK-1
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Disease relevance of LIMK1


High impact information on LIMK1


Biological context of LIMK1


Anatomical context of LIMK1


Associations of LIMK1 with chemical compounds

  • The Myc epitope-tagged LIMK1 and LIMK2 proteins transiently expressed in COS cells exhibited serine/threonine-specific kinase activity toward myelin basic protein and histone in in vitro kinase assay [3].
  • In vitro kinase reaction revealed that the active forms of ROCK phosphorylated LIMK1 on the threonine residue and markedly increased its cofilin-phosphorylating activity [11].
  • MT destabilization induced by thrombin or nocodazole resulted in a decrease of LIMK1 colocalization with MTs [13].
  • A LIMK1 mutant (T508A) with replacement of Thr-508 within the activation loop of the kinase domain by alanine was neither phosphorylated nor activated by ROCK [11].
  • Activation of LIMK1 during mitosis was abrogated by roscovitine, a specific inhibitor of cyclin-dependent kinases (CDKs), suggesting that activation of CDKs directly or indirectly participates in LIMK1 activation [14].

Physical interactions of LIMK1

  • PAK4 was shown to interact specifically with LIMK1 in binding assays [15].
  • We demonstrated that dual regulation of cyclic AMP and Ca2+ determines cofilin (an actin-binding protein) phosphorylation states and LIM kinase 1 (a cofilin kinase) expression level during neuritogenesis [16].
  • Here we demonstrate that p57 regulates actin dynamics by binding and translocating LIMK-1 from the cytoplasm into the nucleus, which in turn results in a reorganization of actin fiber [17].
  • We report here that a RhoA/ROCK/LIM-kinase axis couples the receptor-initiated protein tyrosine kinase activation to the reorganization of the actin cytoskeleton required for the polarization of lipid rafts and the subsequent generation of cell-mediated cytotoxicity [18].
  • Mutation of the CArG box to inhibit YY1 or SRF binding indicated that both factors were required for the LIM kinase response in VSMCs and C2C12 cells [19].

Enzymatic interactions of LIMK1

  • Surprisingly, during shape change cofilin phosphorylation was unaltered, and during aggregation/secretion cofilin was first rapidly dephosphorylated by an okadaic acid-insensitive phosphatase and then slowly rephosphorylated by LIMK-1 [20].
  • PAK-2 activation was accompanied by significant increases in the levels of phosphorylated LIMK and phosphorylated cofilin [21].

Regulatory relationships of LIMK1


Other interactions of LIMK1

  • Par-3 binds to LIMK2 but not to the related kinase LIMK1 [24].
  • Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1 [25].
  • Immunofluorescence experiments revealed that PAK4 and LIMK1 cooperate to induce cytoskeletal changes in C2C12 cells [15].
  • In the antennal lobe, loss of Limk abolishes the ability of p21-activated kinase (Pak) to alter glomerular development [26].
  • We have previously shown that overexpression of LIM kinase1 (LIMK1) resulted in a marked retardation of the internalization of the receptor-mediated endocytic tracer, Texas red-labeled epidermal growth factor (EGF) in low-invasive human breast cancer cell MCF-7 [22].

Analytical, diagnostic and therapeutic context of LIMK1


  1. LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition. Frangiskakis, J.M., Ewart, A.K., Morris, C.A., Mervis, C.B., Bertrand, J., Robinson, B.F., Klein, B.P., Ensing, G.J., Everett, L.A., Green, E.D., Pröschel, C., Gutowski, N.J., Noble, M., Atkinson, D.L., Odelberg, S.J., Keating, M.T. Cell (1996) [Pubmed]
  2. LIM kinase 1 is essential for the invasive growth of prostate epithelial cells: implications in prostate cancer. Davila, M., Frost, A.R., Grizzle, W.E., Chakrabarti, R. J. Biol. Chem. (2003) [Pubmed]
  3. Identification and characterization of a novel family of serine/threonine kinases containing two N-terminal LIM motifs. Okano, I., Hiraoka, J., Otera, H., Nunoue, K., Ohashi, K., Iwashita, S., Hirai, M., Mizuno, K. J. Biol. Chem. (1995) [Pubmed]
  4. LIM kinase 1 increases tumor metastasis of human breast cancer cells via regulation of the urokinase-type plasminogen activator system. Bagheri-Yarmand, R., Mazumdar, A., Sahin, A.A., Kumar, R. Int. J. Cancer (2006) [Pubmed]
  5. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Somlyo, A.P., Somlyo, A.V. Physiol. Rev. (2003) [Pubmed]
  6. LIM-kinase deleted in Williams syndrome. Tassabehji, M., Metcalfe, K., Fergusson, W.D., Carette, M.J., Dore, J.K., Donnai, D., Read, A.P., Pröschel, C., Gutowski, N.J., Mao, X., Sheer, D. Nat. Genet. (1996) [Pubmed]
  7. Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Yang, N., Higuchi, O., Ohashi, K., Nagata, K., Wada, A., Kangawa, K., Nishida, E., Mizuno, K. Nature (1998) [Pubmed]
  8. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Maekawa, M., Ishizaki, T., Boku, S., Watanabe, N., Fujita, A., Iwamatsu, A., Obinata, T., Ohashi, K., Mizuno, K., Narumiya, S. Science (1999) [Pubmed]
  9. Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration. Nishita, M., Tomizawa, C., Yamamoto, M., Horita, Y., Ohashi, K., Mizuno, K. J. Cell Biol. (2005) [Pubmed]
  10. Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes. Tassabehji, M., Metcalfe, K., Karmiloff-Smith, A., Carette, M.J., Grant, J., Dennis, N., Reardon, W., Splitt, M., Read, A.P., Donnai, D. Am. J. Hum. Genet. (1999) [Pubmed]
  11. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. Ohashi, K., Nagata, K., Maekawa, M., Ishizaki, T., Narumiya, S., Mizuno, K. J. Biol. Chem. (2000) [Pubmed]
  12. Role of LIM kinases in normal and psoriatic human epidermis. Honma, M., Benitah, S.A., Watt, F.M. Mol. Biol. Cell (2006) [Pubmed]
  13. LIM kinase 1 coordinates microtubule stability and actin polymerization in human endothelial cells. Gorovoy, M., Niu, J., Bernard, O., Profirovic, J., Minshall, R., Neamu, R., Voyno-Yasenetskaya, T. J. Biol. Chem. (2005) [Pubmed]
  14. Mitosis-dependent phosphorylation and activation of LIM-kinase 1. Sumi, T., Matsumoto, K., Nakamura, T. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  15. Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin. Dan, C., Kelly, A., Bernard, O., Minden, A. J. Biol. Chem. (2001) [Pubmed]
  16. Signal transduction cascades underlying de novo protein synthesis required for neuronal morphogenesis in differentiating neurons. Tojima, T., Ito, E. Prog. Neurobiol. (2004) [Pubmed]
  17. p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus. Yokoo, T., Toyoshima, H., Miura, M., Wang, Y., Iida, K.T., Suzuki, H., Sone, H., Shimano, H., Gotoda, T., Nishimori, S., Tanaka, K., Yamada, N. J. Biol. Chem. (2003) [Pubmed]
  18. A role for a RhoA/ROCK/LIM-kinase pathway in the regulation of cytotoxic lymphocytes. Lou, Z., Billadeau, D.D., Savoy, D.N., Schoon, R.A., Leibson, P.J. J. Immunol. (2001) [Pubmed]
  19. Increased actin polymerization reduces the inhibition of serum response factor activity by Yin Yang 1. Ellis, P.D., Martin, K.M., Rickman, C., Metcalfe, J.C., Kemp, P.R. Biochem. J. (2002) [Pubmed]
  20. Regulation of LIM-kinase 1 and cofilin in thrombin-stimulated platelets. Pandey, D., Goyal, P., Bamburg, J.R., Siess, W. Blood (2006) [Pubmed]
  21. Binding of activated alpha2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK. Misra, U.K., Deedwania, R., Pizzo, S.V. J. Biol. Chem. (2005) [Pubmed]
  22. A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells. Nishimura, Y., Yoshioka, K., Bernard, O., Bereczky, B., Itoh, K. Histochem. Cell Biol. (2006) [Pubmed]
  23. MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration. Kobayashi, M., Nishita, M., Mishima, T., Ohashi, K., Mizuno, K. EMBO J. (2006) [Pubmed]
  24. Par-3 mediates the inhibition of LIM kinase 2 to regulate cofilin phosphorylation and tight junction assembly. Chen, X., Macara, I.G. J. Cell Biol. (2006) [Pubmed]
  25. Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1. Foletta, V.C., Lim, M.A., Soosairajah, J., Kelly, A.P., Stanley, E.G., Shannon, M., He, W., Das, S., Massague, J., Bernard, O., Soosairaiah, J. J. Cell Biol. (2003) [Pubmed]
  26. Lim kinase regulates the development of olfactory and neuromuscular synapses. Ang, L.H., Chen, W., Yao, Y., Ozawa, R., Tao, E., Yonekura, J., Uemura, T., Keshishian, H., Hing, H. Dev. Biol. (2006) [Pubmed]
  27. Inhibition of nuclear import of LIMK2 in endothelial cells by protein kinase C-dependent phosphorylation at Ser-283. Goyal, P., Pandey, D., Behring, A., Siess, W. J. Biol. Chem. (2005) [Pubmed]
  28. Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition. Wang, J.Y., Frenzel, K.E., Wen, D., Falls, D.L. J. Biol. Chem. (1998) [Pubmed]
  29. Xenopus LIM motif-containing protein kinase, Xlimk1, is expressed in the developing head structure of the embryo. Takahashi, T., Aoki, S., Nakamura, T., Koshimizu, U., Matsumoto, K., Nakamura, T. Dev. Dyn. (1997) [Pubmed]
  30. Identification of a human cDNA encoding a novel protein kinase with two repeats of the LIM/double zinc finger motif. Mizuno, K., Okano, I., Ohashi, K., Nunoue, K., Kuma, K., Miyata, T., Nakamura, T. Oncogene (1994) [Pubmed]
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