Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Protein phosphatase Dusp26 associates with KIF3 motor and promotes N-cadherin-mediated cell–cell adhesion

Oncogene volume 28, pages 752–761 (2009)Cite this article

Abstract

Recent studies have demonstrated essential functions for KIF3, a microtubule-directed protein motor, in subcellular transport of several cancer-related proteins, including the β-catenin–cadherin(s) complex. In this study, we report identification of the protein-phosphatase Dusp26 as a novel regulator of the KIF3 motor. Here we undertake yeast two-hybrid screening and identify Kif3a, a motor subunit of the KIF3 heterotrimeric complex, as a novel Dusp26-binding protein. Co-immunoprecipitation and colocalization experiments revealed that Dusp26 associates not only with Kif3a, but also with Kap3, another subunit of the KIF3 complex. Dephosphorylation experiments in vitro and analysis using mutant forms of Dusp26 in intact cells strongly suggested that Dusp26 is recruited to the KIF3 motor mainly by interaction with Kif3a, and thereby dephosphorylates Kap3. Forced expression of Dusp26, but not its catalytically inactive mutant, promoted distribution of β-catenin/N-cadherin, an established KIF3 cargo, to cell–cell junction sites, resulting in increased cell–cell adhesiveness. We also showed that Dusp26 mRNA expression was downregulated in human glioblastoma samples. These results suggest previously unidentified functions of Dusp26 in intracellular transport and cell–cell adhesion. Downregulation of Dusp26 may contribute to malignant phenotypes of glioma.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Alonso A, Sasin J, Bottini N, Friedberg I, Friedberg I, Osterman A et al. (2004). Protein tyrosine phosphatases in the human genome. Cell 117: 699–711.

    Article  CAS  PubMed  Google Scholar 

  • Camps M, Nichols A, Arkinstall S . (2000). Dual specificity phosphatases: a gene family for control of MAP kinase function. FASEB J 14: 6–16.

    Article  CAS  PubMed  Google Scholar 

  • Corbit KC, Shyer AE, Dowdle WE, Gaulden J, Singla V, Chen MH et al. (2008). Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms. Nat Cell Biol 10: 70–76.

    Article  CAS  PubMed  Google Scholar 

  • Guillaud L, Wong R, Hirokawa N . (2008). Disruption of KIF17-Mint1 interaction by CaMKII-dependent phosphorylation: a molecular model of kinesin-cargo release. Nat Cell Biol 10: 19–29.

    Article  CAS  PubMed  Google Scholar 

  • Haraguchi K, Hayashi T, Jimbo T, Yamamoto T, Akiyama T . (2006). Role of the kinesin-2 family protein, KIF3, during mitosis. J Biol Chem 281: 4094–4099.

    Article  CAS  PubMed  Google Scholar 

  • Hirokawa N . (2000a). Determination of Left-Right Asymmetry: Role of Cilia and KIF3 Motor Proteins. News Physiol Sci 15: 56.

    PubMed  Google Scholar 

  • Hirokawa N . (2000b). Stirring up development with the heterotrimeric kinesin KIF3. Traffic 1: 29–34.

    Article  CAS  PubMed  Google Scholar 

  • Hirokawa N, Tanaka Y, Okada Y, Takeda S . (2006). Nodal flow and the generation of left-right asymmetry. Cell 125: 33–45.

    Article  CAS  PubMed  Google Scholar 

  • Hu Y, Mivechi NF. . (2006). Association and regulation of heat shock transcription factor 4b with both extracellular signal-regulated kinase mitogen-activated protein kinase and dual-specificity tyrosine phosphatase DUSP26. Mol Cell Biol 26: 3282–3294.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jimbo T, Kawasaki Y, Koyama R, Sato R, Takada S, Haraguchi K et al. (2002). Identification of a link between the tumour suppressor APC and the kinesin superfamily. Nat Cell Biol 4: 323–327.

    Article  CAS  PubMed  Google Scholar 

  • Karcher RL, Roland JT, Zappacosta F, Huddleston MJ, Annan RS, Carr SA et al. (2001). Cell cycle regulation of myosin-V by calcium/calmodulin-dependent protein kinase II. Science 293: 1317–1320.

    Article  CAS  PubMed  Google Scholar 

  • Kinoshita E, Kinoshita-Kikuta E, Takiyama K, Koike T . (2006). Phosphate-binding tag, a new tool to visualize phosphorylated proteins. Mol Cell Proteomics 5: 749–757.

    Article  CAS  PubMed  Google Scholar 

  • Morita S, Kojima T, Kitamura T . (2000). Plat-E: an efficient and stable system for transient packaging of retroviruses. Gene Ther 7: 1063–1066.

    Article  CAS  PubMed  Google Scholar 

  • Nishimura T, Kato K, Yamaguchi T, Fukata Y, Ohno S, Kaibuchi K . (2004). Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity. Nat Cell Biol 6: 328–334.

    Article  CAS  PubMed  Google Scholar 

  • Ozawa M, Ringwald M, Kemler R . (1990). Uvomorulin–catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc Natl Acad Sci USA 87: 4246–4250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pulido R, Hooft van Huijsduijnen R . (2008). Protein tyrosine phosphatases: dual-specificity phosphatases in health and disease. FEBS J 275: 848–866.

    Article  CAS  PubMed  Google Scholar 

  • Takagaki K, Shima H, Tanuma N, Nomura M, Satoh T, Watanabe M et al. (2007). Characterization of a novel low-molecular-mass dual specificity phosphatase-4 (LDP-4) expressed in brain. Mol Cell Biochem 296: 177–184.

    Article  CAS  PubMed  Google Scholar 

  • Takeda S, Yonekawa Y, Tanaka Y, Okada Y, Nonaka S, Hirokawa N . (1999). Left-right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A-/- mice analysis. J Cell Biol 145: 825–836.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teng J, Rai T, Tanaka Y, Takei Y, Nakata T, Hirasawa M et al. (2005). The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium. Nat Cell Biol 7: 474–482.

    Article  CAS  PubMed  Google Scholar 

  • Vasudevan SA, Skoko J, Wang K, Burlingame SM, Patel PN, Lazo JS et al. (2005). MKP-8, a novel MAPK phosphatase that inhibits p38 kinase. Biochem Biophys Res Commun 330: 511–518.

    Article  CAS  PubMed  Google Scholar 

  • Wang JY, Lin CH, Yang CH, Tan TH, Chen YR . (2006). Biochemical and biological characterization of a neuroendocrine-associated phosphatase. J Neurochem 98: 89–101.

    Article  CAS  PubMed  Google Scholar 

  • Yu W, Imoto I, Inoue J, Onda M, Emi M, Inazawa J . (2007). A novel amplification target, DUSP26, promotes anaplastic thyroid cancer cell growth by inhibiting p38 MAPK activity. Oncogene 26: 1178–1187.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge Dr Konomi Kamada (Hokkaido University, Japan) for kindly providing the plasmid pBTM116-HA, the L40 yeast strain and E. coli HB101, and Dr Toshio Kitamura (University of Tokyo, Japan) for the pMX-puro plasmid and PLAT-E cells. Thanks are also due to E Yoshida for secretarial assistance. This work was supported in part by Grants-in-Aid for Scientific Research (B) and Grants-in-Aid for Scientific Research (C) provided by the Japan Society for the Promotion of Science of Japan.

Author information

Author notes

  1. N Tanuma and M Nomura: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Natori, Japan

    N Tanuma, M Nomura, I Kasugai & H Shima

  2. Division of Biochemical Oncology and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan

    N Tanuma, M Ikeda, Y Tsubaki, K Takagaki & K Kikuchi

  3. Laboratory for Systems Biology and Medicine, RCAST, University of Tokyo, Tokyo, Japan

    T Kawamura

  4. Division of Neurosurgery, Miyagi Cancer Center, Natori, Japan

    Y Yamashita & R Katakura

  5. Section of Clinical Research, Miyagi Cancer Center Research Institute, Natori, Japan

    I Sato

  6. Division of Thoracic Surgery, Miyagi Cancer Center, Natori, Japan

    M Sato

Authors
  1. N Tanuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I Kasugai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y Tsubaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K Takagaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Kawamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. I Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R Katakura
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. K Kikuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. H Shima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H Shima.

Additional information

Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tanuma, N., Nomura, M., Ikeda, M. et al. Protein phosphatase Dusp26 associates with KIF3 motor and promotes N-cadherin-mediated cell–cell adhesion. Oncogene 28, 752–761 (2009). https://doi.org/10.1038/onc.2008.431

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2008.431

Keywords

This article is cited by

Search

Advanced search

Quick links