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 Paper
  • Published:

The EphA8 receptor induces sustained MAP kinase activation to promote neurite outgrowth in neuronal cells

Oncogene volume 24, pages 4243–4256 (2005)Cite this article

Abstract

Recent studies in our laboratory demonstrate that ligand-mediated activation of the EphA8 receptor critically regulates cell adhesion and migration. In this report, we show that the EphA8 receptor induces neurite outgrowth in NG108-15 cells in the absence of ligand stimulation. Using various deletion mutants lacking specific intracytoplasmic regions, we confirm that the tyrosine kinase domain of EphA8 is important for inducing neurite outgrowth. However, the tyrosine kinase activity of EphA8 is not crucial for neurite outgrowth induction. Treatment with various inhibitors further reveals that the mitogen-activated protein kinase (MAPK) signaling pathway is critical for neurite outgrowth induced by EphA8. Consistent with these results, EphA8 expression induced a sustained increase in the activity of MAPK, whereas ligand-mediated EphA8 activation had no further modulatory effects on MAP kinase activity. Additionally, activated MAPK relocalized from the cytoplasm to the nucleus in response to EphA8 transfection. These results collectively suggest that the EphA8 receptor is capable of inducing a sustained increase in MAPK activity, thereby promoting neurite outgrowth in neuronal cells.

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

Similar content being viewed by others

References

  • Becker E, Huynh-Do U, Holland S, Pawson T, Daniel TO and Skolnik EY . (2000). Mol. Cell. Biol., 20, 1537–1545.

  • Choi S, Jeong J, Kim T and Park S . (1999). Mol. Cells, 9, 440–445.

  • Choi S and Park S . (1999). Oncogene, 18, 5413–5422.

  • Coulthard MG, Duffy S, Down M, Evans B, Power M, Smith F, Stylianou C, Kleikamp S, Oates A, Lackmann M, Burns GF and Boyd AW . (2002). Int. J. Dev. Biol., 46, 375–384.

  • Elowe S, Holland SJ, Kulkarni S and Pawson T . (2001). Mol. Cell. Biol., 21, 7429–7441.

  • Gendron L, Oligny JF, Payet MD and Gallo-Payet N . (2003). J. Biol. Chem., 278, 3606–3614.

  • Gu C and Park S . (2001). Mol. Cell. Biol., 21, 4579–4597.

  • Gu C and Park S . (2003). FEBS Lett., 540, 65–70.

  • Himanen JP and Nikolov DB . (2003). Int. J. Biochem. Cell Biol., 35, 130–134.

  • Holland SJ, Gale NW, Gish GD, Roth RA, Songyang Z, Cantley LC, Henkemeyer M, Yancopoulos GD and Pawson T . (1997). EMBO J., 16, 3877–3888.

  • Jeong J, Choi S, Gu C, Lee H and Park S . (2000). DNA Cell Biol., 19, 291–300.

  • Klein R . (2001). Curr. Opin. Cell Biol., 13, 196–203.

  • Koo J, Shim S, Gu C, Yoo O and Park S . (2003). Dev. Dyn., 226, 596–603.

  • Kullander K and Klein R . (2002). Nat. Rev. Mol. Cell Biol., 3, 475–486.

  • Kuo WL, Abe M, Rhee J, Eves EM, McCarthy SA, Yan M, Templeton DJ, McMahon M and Rosner MR . (1996). Mol. Cell. Biol., 16, 1458–1470.

  • Mellitzer G, Xu Q and Wilkinson DG . (2000). Curr. Opin. Neurobiol., 10, 400–408.

  • Miao H, Wei BR, Peehl DM, Li Q, Alexandrou T, Schelling JR, Rhim JS, Sedor JR, Burnett E and Wang B . (2001). Nat. Cell Biol., 3, 527–530.

  • Nelson P, Christian C and Nirenberg M . (1976). Proc. Natl. Acad. Sci. USA, 73, 123–127.

  • Park S, Frisen J and Barbacid M . (1997). EMBO J., 16, 3106–3114.

  • Park S and Sanchez MP . (1997). Oncogene, 14, 533–542.

  • Pratt RL and Kinch MS . (2002). Oncogene, 21, 7690–7699.

  • Schmucker D and Zipursky SL . (2001). Cell, 105, 701–704.

  • Tepass U, Godt D and Winklbauer R . (2002). Curr. Opin. Genet. Dev., 12, 572–582.

  • Tong J, Elowe S, Nash P and Pawson T . (2003). J. Biol. Chem., 278, 6111–6119.

  • Vaudry D, Stork PJ, Lazarovici P and Eiden LE . (2002). Science, 296, 1648–1649.

  • Vindis C, Cerretti DP, Daniel TO and Huynh-Do U . (2003). J. Cell Biol., 162, 661–671.

  • Wilkinson DG . (2001). Nat. Rev. Neurosci., 2, 155–164.

  • Yan M and Templeton DJ . (1994). J. Biol. Chem., 269, 19067–19073.

Download references

Acknowledgements

We thank Dr Henkemeyer for providing a full-length EphB2 cDNA. This work was supported by a Korea Research Foundation Grant (KRF-2002-005-C00014) and also partially by a grant (M103KV010010 03K2201 01030) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology of Republic of Korea.

Author information

Authors and Affiliations

  1. Institute of Natural Science, Sookmyung Women's University, 53-12 Chungpa-Dong 2-Ka, Yongsan-Ku, Seoul, 140-742, Korea

    Changkyu Gu, Sungbo Shim & Jongdae Shin

  2. Department of Genetic Engineering, Hallym University, 1-Okcheon dong, Chuncheon, 200-702, Korea

    Sungbo Shim, Jongdae Shin & Kyuhyung Han

  3. Department of Life Science, Sookmyung Women's University, 53-12 Chungpa-Dong 2-Ka, Yongsan-Ku, Seoul, 140-742, Korea

    Jieun Kim, Jonghoon Park & Soochul Park

Authors
  1. Changkyu Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sungbo Shim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jongdae Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jieun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jonghoon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kyuhyung Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Soochul Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Soochul Park.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gu, C., Shim, S., Shin, J. et al. The EphA8 receptor induces sustained MAP kinase activation to promote neurite outgrowth in neuronal cells. Oncogene 24, 4243–4256 (2005). https://doi.org/10.1038/sj.onc.1208584

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208584

Keywords

This article is cited by

Search

Advanced search

Quick links