Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Ora BernardEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_358


Historical Background

The two members of the LIM kinase (LIMK) family of proteins include LIMK1 and LIMK2. LIMK1, the first of these unique serine kinases to be characterized, was also identified as the murine Kiz-1 protein (Bernard et al. 1994). The second highly related family member, LIMK2, was cloned using a LIMK1 cDNA probe (Okano et al. 1995). These two LIMK family members have identical genomic structures with 16 exons and identical intron/exon boundaries (Bernard et al. 1996; Ikebe et al. 1997). They share a total of ∼50% amino acid sequence identity with ∼70% identity in their kinase domain (Okano et al. 1995). The structure of the LIMK proteins is unique as they contain two different protein–protein interaction domains, namely, LIM (Lin 11, Isl 1, Mec 3) and PDZ (PSD-95, Dlg, ZO-1) domains. Two tandem LIM domains lie at the N-terminal followed by a central PDZ domain. These two domains are separated from the...
This is a preview of subscription content, log in to check access.


  1. Acevedo K, Moussi N, Li R, Soo P, Bernard O. LIM kinase 2 is widely expressed in all tissues. J Histochem Cytochem. 2006;54:487–501.CrossRefPubMedGoogle Scholar
  2. Acevedo K, Li R, Soo P, Suryadinata R, Sarcevic B, Valova VA, Graham ME, Robinson PJ, Bernard O. The phosphorylation of p25/TPPP by LIM kinase 1 inhibits its ability to assemble microtubules. Exp Cell Res. 2007;313:4091–106.CrossRefPubMedGoogle Scholar
  3. Amano T, Tanabe K, Eto T, Narumiya S, Mizuno K. LIM-kinase 2 induces formation of stress fibres, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase- catalysed phosphorylation at threonine-505. Biochem J. 2001;354:149–59.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Arber S, Barbayannis FA, Hanser H, Schneider C, Stanyon CA, Bernard O, Caroni P. Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature. 1998;393:805–9.CrossRefPubMedGoogle Scholar
  5. Bagheri-Yarmand R, Mazumdar A, Sahin AA, Kumar R. LIM kinase 1 increases tumor metastasis of human breast cancer cells via regulation of the urokinase-type plasminogen activator system. Int J Cancer. 2006;118:2703–10.CrossRefPubMedGoogle Scholar
  6. Bamburg JR. Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Annu Rev Cell Dev Biol. 1999;15:185–230.CrossRefPubMedGoogle Scholar
  7. Bernard O, Ganiatsas S, Kannourakis G, Dringen R. Kiz-1, a protein with LIM zinc finger and kinase domains, is expressed mainly in neurons. Cell Growth Differ. 1994;5:1159–71.PubMedGoogle Scholar
  8. Bernard O, Burkitt V, Webb GC, Bottema CD, Nicholl J, Sutherland GR, Matthew P. Structure and chromosomal localization of the genomic locus encoding the Kiz1 LIM-kinase gene. Genomics. 1996;35:593–6.CrossRefPubMedGoogle Scholar
  9. Dan C, Kelly A, Bernard O, Minden A. Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin. J Biol Chem. 2001;276:32115–21.CrossRefPubMedGoogle Scholar
  10. Davila M, Frost AR, Grizzle WE, Chakrabarti R. LIM kinase 1 is essential for the invasive growth of prostate epithelial cells: implications in prostate cancer. J Biol Chem. 2003;278:36868–75.CrossRefPubMedGoogle Scholar
  11. Edwards DC, Gill GN. Structural features of LIM kinase that control effects on the actin cytoskeleton. J Biol Chem. 1999;274:11352–61.CrossRefPubMedGoogle Scholar
  12. Edwards DC, Sanders LC, Bokoch GM, Gill GN. Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol. 1999;1:253–9.CrossRefPubMedGoogle Scholar
  13. Foletta VC, Moussi N, Sarmiere PD, Bamburg JR, Bernard O. LIM kinase 1, a key regulator of actin dynamics, is widely expressed in embryonic and adult tissues. Exp Cell Res. 2004;294:392–405.CrossRefPubMedGoogle Scholar
  14. Gohla A, Birkenfeld J, Bokoch GM. Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics. Nat Cell Biol. 2005;7:21–9.CrossRefPubMedGoogle Scholar
  15. Gorovoy M, Niu J, Bernard O, Profirovic J, Minshall R, Neamu R, Voyno-Yasenetskaya T. LIM kinase 1 coordinates microtubule stability and actin polymerization in human endothelial cells. J Biol Chem. 2005;280:26533–42.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Hsu FF, Lin TY, Chen JY, Shieh SY. p53-Mediated transactivation of LIMK2b links actin dynamics to cell cycle checkpoint control. Oncogene. 2010;29:2864–76.CrossRefPubMedGoogle Scholar
  17. Ikebe C, Ohashi K, Fujimori T, Bernard O, Noda T, Robertson EJ, Mizuno K. Mouse LIM-kinase 2 gene – cDNA cloning, genomic organization, and tissue-specific expression of two alternatively initiated transcripts. Genomics. 1997;46:504–8.CrossRefPubMedGoogle Scholar
  18. Kaji N, Muramoto A, Mizuno K. LIM kinase-mediated cofilin phosphorylation during mitosis is required for precise spindle positioning. J Biol Chem. 2008;283:4983–92.CrossRefPubMedGoogle Scholar
  19. Li R, Soosairajah J, Harari D, Citri A, Price J, Ng HL, Morton CJ, Parker MW, Yarden Y, Bernard O. Hsp90 increases LIM kinase activity by promoting its homo-dimerization. FASEB J. 2006;20:1218–20.CrossRefPubMedGoogle Scholar
  20. Misra UK, Deedwania R, Pizzo SV. Binding of activated alpha2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK. J Biol Chem. 2005;280:26278–86.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Mizuno K, Okano I, Ohashi K, Nunoue K, Kuma K, Miyata T, Nakamura T. Identification of a human cDNA encoding a novel protein kinase with two repeats of the LIM/double zinc finger motif. Oncogene. 1994;9:1605–12.PubMedGoogle Scholar
  22. Moriyama K, Iida K, Yahara I. Phosphorylation of Ser-3 of cofilin regulates its essential function on actin. Genes Cells. 1996;1:73–86.CrossRefPubMedGoogle Scholar
  23. Nebl G, Meuer SC, Samstag Y. Dephosphorylation of serine 3 regulates nuclear translocation of cofilin. J Biol Chem. 1996;271:26276–80.CrossRefPubMedGoogle Scholar
  24. Niwa R, Nagata-Ohashi K, Takeichi M, Mizuno K, Uemura T. Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell. 2002;108:233–46.CrossRefPubMedGoogle Scholar
  25. Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem. 2000;275:3577–82.CrossRefPubMedGoogle Scholar
  26. Okano I, Hiraoka J, Otera H, Nunoue K, Ohashi K, Iwashita S, Hirai M, Mizuno K. Identification and characterization of a novel family of serine/threonine kinases containing two N-terminal LIM motifs. J Biol Chem. 1995;270:31321–30.CrossRefPubMedGoogle Scholar
  27. Sacchetti P, Carpentier R, Segard P, Olive-Cren C, Lefebvre P. Multiple signaling pathways regulate the transcriptional activity of the orphan nuclear receptor NURR1. Nucleic Acids Res. 2006;34:5515–27.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Scott RW, Hooper S, Crighton D, Li A, Konig I, Munro J, Trivier E, Wickman G, Morin P, Croft DR, Dawson J, Machesky L, Anderson KI, Sahai EA, Olson MF. LIM kinases are required for invasive path generation by tumor and tumor-associated stromal cells. J Cell Biol. 2010;191:169–85.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Soosairajah J, Maiti S, Wiggan O, Sarmiere P, Moussi N, Sarcevic B, Sampath R, Bamburg JR, Bernard O. Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005;24:473–86.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Stanyon CA, Bernard O. LIM-kinase1. Int J Biochem Cell Biol. 1999;31:389–94.CrossRefPubMedGoogle Scholar
  31. Sumi T, Matsumoto K, Nakamura T. Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase. J Biol Chem. 2001a;276:670–6.CrossRefPubMedGoogle Scholar
  32. Sumi T, Matsumoto K, Shibuya A, Nakamura T. Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha. J Biol Chem. 2001b;276:23092–6.CrossRefPubMedGoogle Scholar
  33. Sumi T, Hashigasako A, Matsumoto K, Nakamura T. Different activity regulation and subcellular localization of LIMK1 and LIMK2 during cell cycle transition. Exp Cell Res. 2006;312:1021–30.CrossRefPubMedGoogle Scholar
  34. Takahashi H, Koshimizu U, Miyazaki J, Nakamura T. Impaired spermatogenic ability of testicular germ cells in mice deficient in the LIM-kinase 2 gene. Dev Biol. 2002;241:259–72.CrossRefPubMedGoogle Scholar
  35. Tapia T, Ottman R, Chakrabarti R. LIM kinase1 modulates function of membrane type matrix metalloproteinase 1: implication in invasion of prostate cancer cells. Mol Cancer. 2011;10:6.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Vlecken DH, Bagowski CP. LIMK1 and LIMK2 are important for metastatic behavior and tumor cell-induced angiogenesis of pancreatic cancer cells. Zebrafish. 2009;6:433–9.CrossRefPubMedGoogle Scholar
  37. Wang W, Goswami S, Lapidus K, Wells AL, Wyckoff JB, Sahai E, Singer RH, Segall JE, Condeelis JS. Identification and testing of a gene expression signature of invasive carcinoma cells within primary mammary tumors. Cancer Res. 2004;64:8585–94.CrossRefPubMedGoogle Scholar
  38. Yang N, Higuchi O, Ohashi K, Nagata K, Wada A, Kangawa K, Nishidi E, Mizuno K. Cofilin phosphorylation by LIM-kinase1 and its role in Rac-mediated actin reorganization. Nature. 1998;393:809–12.CrossRefPubMedGoogle Scholar
  39. Yang EJ, Yoon JH, Min DS, Chung KC. LIM kinase 1 activates cAMP-responsive element-binding protein during the neuronal differentiation of immortalized hippocampal progenitor cells. J Biol Chem. 2004;279:8903–10.CrossRefPubMedGoogle Scholar
  40. Yoshioka K, Foletta V, Bernard O, Itoh K. A role for LIM kinase in cancer invasion. Proc Natl Acad Sci U S A. 2003;100:7247–52.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Cytoskeleton and Cancer UnitSt Vincent’s Institute of Medical ResearchFitzroyAustralia