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:

Protein kinase D complexes with C-Jun N-terminal kinase via activation loop phosphorylation and phosphorylates the C-Jun N-terminus

Oncogene volume 21, pages 2154–2160 (2002)Cite this article

Abstract

Protein kinase D (PKD), a downstream effector of protein kinase C (PKC), is implicated in suppression of the c-Jun N-terminal kinase (JNK) signaling pathway, however, its mechanism of action is unclear. Transphosphorylation of the PKD activation loop at serines 744/748 by a PKC mediated signal transduction pathway enhances its catalytic activity. Here we show that PKD activation loop phosphorylation at serines 744/748 via PKC, or mutation of these serines to glutamic acid (PKD-S744/748E) also results in complex formation with JNK, indicating that suppression of JNK signaling by PKD involves a direct interaction with JNK. Because catalytically active PKD associates with JNK we determined whether it could phosphorylate the c-Jun N-terminus as a potential mechanism by which it suppresses c-Jun Ser 63 phosphorylation when it complexes with JNK. Purified human PKD and either wild-type PKD from phorbol 12, 13-dibutyrate (PDB)-stimulated cells or unstimulated constitutively active PKD (PKD-S744/748E), phosphorylated the c-Jun N-terminus between amino acids 1–89 at sites distinct from those phosphorylated by JNK. These results demonstrate, for the first time, phosphorylation dependent association of PKD with another signaling molecule and reveal a potential mechanism by which PKD could modulate the ability of JNK to phosphorylate c-Jun by phosphorylating alternative sites in the c-Jun N-terminus when it is complexed with JNK.

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

Similar content being viewed by others

References

  • Akkaraju GR, Basu A . 2000 Biochem. Biophys. Res. Commun. 279: 103–107

  • Bagowski CP, Stein-Gerlach M, Choidas A, Ullrich A . 1999 EMBO J. 18: 5567–5576

  • Basu A, Mohanty S, Sun B . 2001 Biochem. Biophys. Res. Commun. 280: 883–891

  • Bowden ET, Barth M, Thomas D, Glazer RI, Mueller SC . 1999 Oncogene 18: 4440–4449

  • Chen CY, Liou J, Forman LW, Faller DV . 1998 J. Biol. Chem. 273: 16700–16709

  • Davis RJ . 2000 Cell 103: 239–252

  • Guo BC, Xu YH . 2001 Cell Res. 11: 101–106

  • Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Derijard B, Davis RJ . 1996 EMBO J. 15: 2760–2770

  • Hausser A, Storz P, Link G, Stoll H, Liu YC, Altman A, Pfizenmaier K, Johannes FJ . 1999 J. Biol. Chem. 274: 9258–9264

  • Hurd C, Rozengurt E . 2001 Biochem. Biophys. Res. Commun. 282: 404–408

  • Iglesias T, Cabrera-Poch N, Mitchell MP, Naven TJ, Rozengurt E, Schiavo G . 2000 J. Biol. Chem. 275: 40048–40056

  • Iglesias T, Waldron RT, Rozengurt E . 1998 J. Biol. Chem. 273: 27662–27667

  • Johannes FJ, Hausser A, Storz P, Truckenmuller L, Link G, Kawakami T, Pfizenmaier K . 1999 FEBS Lett. 461: 68–72

  • Johannes FJ, Horn J, Link G, Haas E, Siemienski K, Wajant H, Pfizenmaier K . 1998 Eur. J. Biochem. 257: 47–54

  • Johannes FJ, Prestle J, Eis S, Oberhagemann P, Pfizenmaier K . 1994 J. Biol. Chem. 269: 6140–6148

  • Kallunki T, Deng T, Hibi M, Karin M . 1996 Cell 87: 929–939

  • Kallunki T, Su B, Tsigelny I, Sluss HK, Derijard B, Moore G, Davis R, Karin M . 1994 Genes. Dev. 8: 2996–3007

  • Matthews SA, Pettit GR, Rozengurt E . 1997 J. Biol. Chem. 272: 20245–20250

  • Matthews SA, Rozengurt E, Cantrell D . 2000 J. Exp. Med. 191: 2075–2082

  • Nishikawa K, Toker A, Wong K, Marignani PA, Johannes FJ, Cantley LC . 1998 J. Biol. Chem. 273: 23126–23133

  • Paolucci L, Sinnett-Smith J, Rozengurt E . 2000 Am. J. Physiol. Cell. Physiol. 278: C33–C39

  • Ruiz-Ruiz C, Robledo G, Font J, Izquierdo M, Lopez-Rivas A . 1999 J. Immunol. 163: 4737–4746

  • Shinohara H, Kayagaki N, Yagita H, Oyaizu N, Ohba M, Kuroki T, Ikawa Y . 2001 Biochem. Biophys. Res. Commun. 284: 1162–1167

  • Sidorenko SP, Law CL, Klaus SJ, Chandran KA, Takata M, Kurosaki T, Clark EA . 1996 Immunity 5: 353–363

  • Smeal T, Binetruy B, Mercola DA, Birrer M, Karin M . 1991 Nature 354: 494–496

  • Storz P, Hausser A, Link G, Dedio J, Ghebrehiwet B, Pfizenmaier K, Johannes FJ . 2000 J. Biol. Chem. 275: 24601–24607

  • Tanoue T, Adachi M, Moriguchi T, Nishida E . 2000 Nat. Cell. Biol. 2: 110–116

  • Trauzold A, Wermann H, Arlt A, Schutze S, Schafer H, Oestern S, Roder C, Ungefroren H, Lampe E, Heinrich M, Walczak H, Kalthoff H . 2001 Oncogene. 20: 4258–4269

  • Valverde AM, Sinnett-Smith J, Van Lint J, Rozengurt E . 1994 Proc. Natl. Acad. Sci. USA 91: 8572–8576

  • Waldron RT, Iglesias T, Rozengurt E . 1999a Electrophoresis 20: 382–390

  • Waldron RT, Iglesias T, Rozengurt E . 1999b J. Biol. Chem. 274: 9224–9230

  • Waldron RT, Rey O, Iglesias T, Tugal T, Cantrell D, Rozengurt E . 2001 J. Biol. Chem. 276: 32606–32615

  • Waldron RT, Rozengurt E . 2000 J. Biol. Chem. 275: 17114–17121

  • Yuan J, Slice L, Walsh JH, Rozengurt E . 2000 J. Biol. Chem. 275: 2157–2164

  • Zhukova E, Sinnett-Smith J, Rozengurt E . 2001 J. Biol. Chem. 20: 20–

  • Zugaza JL, Sinnett-Smith J, Van Lint J, Rozengurt E . 1996 EMBO J. 15: 6220–6230

  • Zugaza JL, Waldron RT, Sinnett-Smith J, Rozengurt E . 1997 J. Biol. Chem. 272: 23952–23960

Download references

Acknowledgements

We thank J Sinnett-Smith and O Rey for helpful discussions and R Chiu for providing the HA-JNK1 expression plasmid. This work was supported by National Institutes of Health Grants DK55003, DK56930 and National Cancer Institute Grant P50 CA90388-01. R Waldron is the recipient of a Mentored Research Scientist Career Development Award, K01 DK 02834-01. E Rozengurt is the Ronald S. Hirshberg Professor of Translational Pancreatic Cancer Research.

Author information

Authors and Affiliations

  1. Division of Digestive Diseases, Department of Medicine, Unit of Signal Transduction and Gastrointestinal Cancer, School of Medicine and Molecular Biology Institute, University of California, Los Angeles, 90095, USA, California, CA

    Cliff Hurd, Richard T Waldron & Enrique Rozengurt

Authors
  1. Cliff Hurd
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard T Waldron
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Enrique Rozengurt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Enrique Rozengurt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hurd, C., Waldron, R. & Rozengurt, E. Protein kinase D complexes with C-Jun N-terminal kinase via activation loop phosphorylation and phosphorylates the C-Jun N-terminus. Oncogene 21, 2154–2160 (2002). https://doi.org/10.1038/sj.onc.1205290

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205290

Keywords

This article is cited by

Search

Advanced search

Quick links