Skip to main content
SpringerLink
Log in
Book cover

Encyclopedia of Signaling Molecules pp 2878–2885Cite as

LIMK

  • Reference work entry
  • First Online:

  • 120 Accesses

Synonyms

Isl 1; Kiz; LIM kinase; Lin 11; Mec 3 (LIM) kinase

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 kinase...

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Bamburg JR. Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Annu Rev Cell Dev Biol. 1999;15:185–230.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Edwards DC, Gill GN. Structural features of LIM kinase that control effects on the actin cytoskeleton. J Biol Chem. 1999;274:11352–61.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • Moriyama K, Iida K, Yahara I. Phosphorylation of Ser-3 of cofilin regulates its essential function on actin. Genes Cells. 1996;1:73–86.

    Article  CAS  PubMed  Google Scholar 

  • Nebl G, Meuer SC, Samstag Y. Dephosphorylation of serine 3 regulates nuclear translocation of cofilin. J Biol Chem. 1996;271:26276–80.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stanyon CA, Bernard O. LIM-kinase1. Int J Biochem Cell Biol. 1999;31:389–94.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cytoskeleton and Cancer Unit, St Vincent’s Institute of Medical Research, 9 Princes St, Fitzroy, VIC, 3065, Australia

    Ora Bernard

Authors
  1. Ora Bernard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ora Bernard .

Editor information

Editors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Bernard, O. (2018). LIMK. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_358

Download citation

Publish with us

Policies and ethics

Search

Navigation