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:

ZPK inhibits PKA induced transcriptional activation by CREB and blocks retinoic acid induced neuronal differentiation

Oncogene volume 18, pages 4474–4484 (1999)Cite this article

Abstract

Zipper Protein Kinase (ZPK) is a leucine zipper protein localized to the nucleus which exhibits serine-threonine kinase activity and is associated with the stress dependent signal transduction pathway. ZPK forms heterodimers with leucine zipper containing transcription factors such as the cyclic AMP responsive element binding protein (CREB) and Myc. Furthermore ZPK phosphorylates both Myc and CREB. Overexpression of ZPK in NTera-2 human teratocarcinoma cells results in inhibition of PKA induced transcriptional activation by CREB and prevents retinoic acid induced differentiation of the cells to neurons. Our results suggest that ZPK stifles neural differentiation of NT-2 cells partly due to its inhibitory effect on CREB function.

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

Abbreviations

CREB:

cAMP response element binding protein

ZPK:

zipper protein kinase

CRE:

cAMP response element

RA:

retinoic acid

PKA:

protein kinase A

References

  • Abraham I, Sampson KE, Powers EA, Mayo JK, Ruff VA and Leach KL. . 1991 J. Neurol. Res. 28: 29–39.

  • Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman IG, Smith JA and Struhl K. . 1996 In: Current Protocols in Molecular Biology. Vol.3. John Wiley Sons, Inc.

    Google Scholar 

  • Brindle P, Linke S and Montminy M. . 1993 Nature (Lond.) 364: 821–824.

  • Cheung WMW, Chu AH, Leung M-F, Ip NY. . 1996 Neuroreport 7: 1204–1208.

  • Evans GI, Lewis GK, Ramsay G and Bishop VM. . 1985 Mol. Cell. Biol. 5: 3610–3616.

  • Fan G, Merritt SE, Kortenjann M, Shaw PE and Holzman LB. . 1996 J. Biol. Chem. 271: 24788–24793.

  • Gonzalez GA and Montminy MR. . 1989 Cell 59: 675–680.

  • Hagiwara M, Brindle P, Harootunian A, Armstrong R, River J, Vale W, Tsien R and Montminy MR. . 1993 Mol. Cell. Biol. 13: 4852–4859.

  • Hai T, Liu F, Coukos WJ and Green MR. . 1989 Genes Dev. 3: 2083.

  • Harlow E and Lane D. . 1988 In: Antibodies: A Laboratory Manual. Cold Spring Harbor Laboratory: Cold Spring Harbor, New York.

    Google Scholar 

  • Hirai S-I, Izawa M, Osada S-I, Spyrou G and Ohno S. . 1996 Oncogene 12: 641–650.

  • Hirai S-I, Katoh M, Terada M, Kyriakis JM, Zon LI, Rana A, Avruch J and Ohno S. . 1997 J. Biol. Chem. 272: 15167–15173.

  • Holzman LB, Merritt SE and Fan G. . 1994 J. Biol. Chem. 269: 30808–30817.

  • Ikegaki N, Butovsky J and Kennett RH. . 1986 Proc. Natl. Acad. Sci. USA 83: 5929–5933.

  • Johnson PF and McKnight SL. . 1989 Ann. Rev. Biochem. 58: 799–839.

  • Kawai T, Matsumoto M, Takeda K, Sanjo H and Akira S. . 1998 Mol. Cell. Biol. 18: 1642–1651.

  • Lee KAW and Masson N. . 1993 Biochem. Biophys. Acta 1174: 221–233.

  • Liu F and Green MR. . 1990 Cell 61: 1217.

  • Martin KC and Kandel ER. . 1996 Neuron 17: 567–570.

  • Mata M, Merritt SE, Fan G, Yu GG and Holzman LB. . 1996 J. Biol. Chem. 271: 16888–16896.

  • Miller AD and Buttimore C. . 1986 Mol. Cell. Biol. 6: 2895–2902.

  • Mochly-Rosen D. . 1995 Science 268: 247–251.

  • O'Shea EK, Rutkowski R, Stafford III WF and Kim PS. . 1989 Science 245: 646–648.

  • Pleasure SJ, Page C and Lee VM-Y. . 1992 J. Neurosci 12: 1802–1815.

  • Reddy UR and Pleasure D. . 1994 Biochem. Biophys. Res. Comm. 202: 613–620.

  • Schrieber E, Matthias P, Muller MM and Schaffner W. . 1989 Nucl. Acid Res. 17: 6419.

  • Stockschlaeder MAR, Storb R, Osborne WRA and Miller DA. . 1991 Hum. Gene. Therapy 2: 33–39.

  • Sun P, Enslen H, Myung PS and Maurer R. . 1994 Genes Dev. 8: 2527–2539.

  • Wigler M, Pellicer A, Silverstein S and Axel R. . 1978 Cell 14: 725–731.

Download references

Acknowledgements

We thank Marge Williams for technical assistance with NT2 cell differentiation and Dr Montminy for providing the recombinant full length CREB. This work was supported in part by grants from the National Institute of Health (NS25044, NS08075, NS31102) and Muscular Dystrophy Association.

Author information

Authors and Affiliations

  1. Department of Neurology Research, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, Pennsylvania, USA

    Usha R Reddy, Peter Bannerman & David Pleasure

  2. Department of Oncology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, Pennsylvania, USA

    Naohiko Ikegaki

  3. Department of Neuro-Oncology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, Pennsylvania, USA

    C Damodara Reddy

  4. The Wistar Institute, Philadelphia, PA 19104, Pennsylvania, USA

    Amitabha Basu

Authors
  1. Usha R Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amitabha Basu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Bannerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naohiko Ikegaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Damodara Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David Pleasure
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reddy, U., Basu, A., Bannerman, P. et al. ZPK inhibits PKA induced transcriptional activation by CREB and blocks retinoic acid induced neuronal differentiation. Oncogene 18, 4474–4484 (1999). https://doi.org/10.1038/sj.onc.1202813

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202813

Keywords

This article is cited by

Search

Advanced search

Quick links