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:

Essential roles of ERK-mediated phosphorylation of vinexin in cell spreading, migration and anchorage-independent growth

Oncogene volume 26, pages 7122–7131 (2007)Cite this article

Abstract

Vinexin is an adaptor protein supposed to play pivotal roles in various cellular events such as cell adhesion, cytoskeletal organization, signaling and gene expression. Despite the possible importance, physiological functions and regulatory mechanisms of vinexin are largely unknown. In addition, although vinexin was reported to be phosphorylated by extracellular signal-regulated kinase (ERK), physiological significance of the phosphorylation remains to be elucidated. Here we carried out characterization of endogenous vinexin and found that it was enriched at the leading edge of migrating cells and focal adhesions of spread cells. In the analyses using ERK-phosphorylated vinexin-specific antibody, the phosphorylation signal was also detected at the leading edges of migrating cells and at cell periphery of spreading cells, whereas only faint signal was observed at focal adhesions of well-spread cells. We then established LNCaP cell lines stably expressing GFP-fused vinexinβ or two mutants at Ser189 that mimic the ERK-phosphorylated or -unphosphorylated vinexinβ. Based on the analyses using the lines, the phosphorylation was likely to inhibit the cell spreading and migration. On the other hand, anchorage-independent cell growth was inhibited by unphosphorylated vinexinβ. Taken together, ERK-mediated phosphorylation of vinexinβ is strongly suggested to occur in a spatio-temporally regulated manner and play important roles in cell spreading, migration and anchorage-independent growth.

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
Figure 8
Figure 9

Similar content being viewed by others

References

  • Akamatsu M, Aota S, Suwa A, Ueda K, Amachi T, Yamada KM et al. (1999). Vinexin forms a signaling complex with Sos and modulates epidermal growth factor-induced c-Jun N-terminal kinase/stress-activated protein kinase activities. J Biol Chem 274: 35933–35937.

    Article  CAS  Google Scholar 

  • Bour G, Plassat JL, Bauer A, Lalevee S, Rochette-Egly C . (2005). Vinexinβ interacts with the non-phosphorylated AF-1 domain of retinoid receptorγ (RAR γ) and represses RAR γ-mediated transcription. J Biol Chem 280: 17027–17037.

    Article  CAS  Google Scholar 

  • Huang C, Jacobson K, Schaller MD . (2004). MAP kinases and cell migration. J Cell Sci 117: 4619–4628.

    Article  CAS  Google Scholar 

  • Ito H, Usuda N, Atsuzawa K, Iwamoto I, Sudo K, Katoh-Semba R et al. (2007). Phosphorylation by extracellular signal-regulated kinase of a multidomain adaptor protein, vinexin, at synapses. J Neurochem 100: 545–554.

    Article  CAS  Google Scholar 

  • Kioka N, Sakata S, Kawauchi T, Amachi T, Akiyama SK, Okazaki K et al. (1999). Vinexin: a novel vinculin-binding protein with multiple SH3 domains enhances actin cytoskeletal organization. J Cell Biol 144: 59–69.

    Article  CAS  Google Scholar 

  • Kioka N, Ueda K, Amachi T . (2002). Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction. Cell Struct Funct 27: 1–7.

    Article  CAS  Google Scholar 

  • Matsuyama M, Mizusaki H, Shimono A, Mukai T, Okumura K, Abe K et al. (2005). A novel isoform of Vinexin, Vinexin gamma, regulates Sox9 gene expression through activation of MAPK cascade in mouse fetal gonad. Genes Cells 10: 421–434.

    Article  CAS  Google Scholar 

  • Mitsushima M, Sezaki T, Akahane R, Ueda K, Suetsugu S, Takenawa T et al. (2006). Protein kinase A-dependent increase in WAVE2 expression induced by the focal adhesion protein vinexin. Genes Cells 11: 281–292.

    Article  CAS  Google Scholar 

  • Mitsushima M, Suwa A, Amachi T, Ueda K, Kioka N . (2004). Extracellular signal-regulated kinase activated by epidermal growth factor and cell adhesion interacts with and phosphorylates vinexin. J Biol Chem 279: 34570–34577.

    Article  CAS  Google Scholar 

  • Nagata K, Asano T, Nozawa Y, Inagaki M . (2004). Biochemical and cell biological analyses of a mammalian septin complex, Sept7/9b/11. J Biol Chem 279: 55895–55904.

    Article  CAS  Google Scholar 

  • Suwa A, Mitsushima M, Ito T, Akamatsu M, Ueda K, Amachi T et al. (2002). Vinexin beta regulates the anchorage dependence of ERK2 activation stimulated by epidermal growth factor. J Biol Chem 277: 13053–13058.

    Article  CAS  Google Scholar 

  • Takahashi H, Mitsushima M, Okada N, Ito T, Aizawa S, Akahane R et al. (2005). Role of interaction with vinculin in recruitment of vinexins to focal adhesions. Biochem Biophys Res Commun 336: 239–246.

    Article  CAS  Google Scholar 

  • Tujague M, Thomsen JS, Mizuki K, Sadek CM, Gustafsson JA . (2004). The focal adhesion protein vinexin alpha regulates the phosphorylation and activity of estrogen receptor alpha. J Biol Chem 279: 9255–9263.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants-in-aid for scientific research from Ministry of Education, Science, Technology, Sports and Culture of Japan, grants from Takeda Science Foundation and Aichi Cancer Research Foundation.

Author information

Authors and Affiliations

  1. Department of Urology, Gifu University School of Medicine, 1-1 Yanagido, Gifu, Japan

    K Mizutani & T Deguchi

  2. Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan

    H Ito, I Iwamoto, R Morishita, T Asano & K-i Nagata

  3. Gifu International Institute of Biotechnology, 1-1 Nakafudogaoka, Gifu, Japan

    K Mizutani & Y Nozawa

Authors
  1. K Mizutani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I Iwamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Morishita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Deguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y Nozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Asano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K-i Nagata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K-i Nagata.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mizutani, K., Ito, H., Iwamoto, I. et al. Essential roles of ERK-mediated phosphorylation of vinexin in cell spreading, migration and anchorage-independent growth. Oncogene 26, 7122–7131 (2007). https://doi.org/10.1038/sj.onc.1210512

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1210512

Keywords

This article is cited by

Search

Advanced search

Quick links