This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Seternes, O. M.
Right arrow Articles by Moens, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seternes, O. M.
Right arrow Articles by Moens, U.

Next Article 

Molecular and Cellular Biology, October 2002, p. 6931-6945, Vol. 22, No. 20
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.20.6931-6945.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Both Binding and Activation of p38 Mitogen-Activated Protein Kinase (MAPK) Play Essential Roles in Regulation of the Nucleocytoplasmic Distribution of MAPK-Activated Protein Kinase 5 by Cellular Stress

Ole Morten Seternes,1* Bjarne Johansen,2 Beate Hegge,2 Mona Johannessen,2 Stephen M. Keyse,3 and Ugo Moens2

Department of Biochemistry,2 Department of Pharmacology, Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway,1 Cancer Research UK, Molecular Pharmacology Unit, Biomedical Research Centre, Ninewells Hospital, Dundee DD1 9SY, Scotland3

Received 18 April 2002/ Returned for modification 29 May 2002/ Accepted 8 July 2002

The p38 mitogen-activated protein kinase (MAPK) pathway is an important mediator of cellular responses to environmental stress. Targets of p38 include transcription factors, components of the translational machinery, and downstream serine/threonine kinases, including MAPK-activated protein kinase 5 (MK5). Here we have used enhanced green fluorescent protein fusion proteins to analyze the subcellular localization of MK5. Although this protein is predominantly nuclear in unstimulated cells, MK5 shuttles between the nucleus and the cytoplasm. Furthermore, we have shown that the C-terminal domain of MK5 contains both a functional nuclear localization signal (NLS) and a leucine-rich nuclear export signal (NES), indicating that the subcellular distribution of this kinase reflects the relative activities of these two signals. In support of this, we have shown that stress-induced activation of the p38 MAPK stimulates the chromosomal region maintenance 1 protein-dependent nuclear export of MK5. This is regulated by both binding of p38 MAPK to MK5, which masks the functional NLS, and stress-induced phosphorylation of MK5 by p38 MAPK, which either activates or unmasks the NES. These properties may define the ability of MK5 to differentially phosphorylate both nuclear and cytoplasmic targets or alternatively reflect a mechanism whereby signals initiated by activation of MK5 in the nucleus may be transmitted to the cytoplasm.

* Corresponding author. Mailing address: University of Tromsø, Institute of Medical Biology, Department of Pharmacology, N-9037 Tromsø, Norway. Phone: 47 77 64 53 42. Fax: 47 77 64 5310. e-mail: olems{at}fagmed.uit.no.

Molecular and Cellular Biology, October 2002, p. 6931-6945, Vol. 22, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.20.6931-6945.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Aberg, E., Torgersen, K. M., Johansen, B., Keyse, S. M., Perander, M., Seternes, O.-M. (2009). Docking of PRAK/MK5 to the Atypical MAPKs ERK3 and ERK4 Defines a Novel MAPK Interaction Motif. J. Biol. Chem. 284: 19392-19401 [Abstract] [Full Text]  
  • Gerits, N., Mikalsen, T., Kostenko, S., Shiryaev, A., Johannessen, M., Moens, U. (2007). Modulation of F-actin Rearrangement by the Cyclic AMP/cAMP-dependent Protein Kinase (PKA) Pathway Is Mediated by MAPK-activated Protein Kinase 5 and Requires PKA-induced Nuclear Export of MK5. J. Biol. Chem. 282: 37232-37243 [Abstract] [Full Text]  
  • Johannessen, M., Delghandi, M. P., Rykx, A., Dragset, M., Vandenheede, J. R., Van Lint, J., Moens, U. (2007). Protein Kinase D Induces Transcription through Direct Phosphorylation of the cAMP-response Element-binding Protein. J. Biol. Chem. 282: 14777-14787 [Abstract] [Full Text]  
  • Harris, J. E., Fernandez-Vilaseca, M., Elkington, P. T. G., Horncastle, D. E., Graeber, M. B., Friedland, J. S. (2007). IFN{gamma} synergizes with IL-1{beta} to up-regulate MMP-9 secretion in a cellular model of central nervous system tuberculosis. FASEB J. 21: 356-365 [Abstract] [Full Text]  
  • Aberg, E., Perander, M., Johansen, B., Julien, C., Meloche, S., Keyse, S. M., Seternes, O.-M. (2006). Regulation of MAPK-activated Protein Kinase 5 Activity and Subcellular Localization by the Atypical MAPK ERK4/MAPK4. J. Biol. Chem. 281: 35499-35510 [Abstract] [Full Text]  
  • Kant, S., Schumacher, S., Singh, M. K., Kispert, A., Kotlyarov, A., Gaestel, M. (2006). Characterization of the Atypical MAPK ERK4 and Its Activation of the MAPK-activated Protein Kinase MK5. J. Biol. Chem. 281: 35511-35519 [Abstract] [Full Text]  
  • Makino, C., Sano, Y., Shinagawa, T., Millar, J. B. A., Ishii, S. (2006). Sin1 binds to both ATF-2 and p38 and enhances ATF-2-dependent transcription in an SAPK signaling pathway. GENES CELLS 11: 1239-1251 [Abstract] [Full Text]  
  • Fu, J., Yang, Z., Wei, J., Han, J., Gu, J. (2006). Nuclear protein NP60 regulates p38 MAPK activity. J. Cell Sci. 119: 115-123 [Abstract] [Full Text]  
  • DeVries-Seimon, T., Li, Y., Yao, P. M., Stone, E., Wang, Y., Davis, R. J., Flavell, R., Tabas, I. (2005). Cholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptor. JCB 171: 61-73 [Abstract] [Full Text]  
  • Hildesheim, J., Salvador, J. M., Hollander, M. C., Fornace, A. J. Jr. (2005). Casein Kinase 2- and Protein Kinase A-regulated Adenomatous Polyposis Coli and {beta}-Catenin Cellular Localization Is Dependent on p38 MAPK. J. Biol. Chem. 280: 17221-17226 [Abstract] [Full Text]  
  • Voncken, J. W., Niessen, H., Neufeld, B., Rennefahrt, U., Dahlmans, V., Kubben, N., Holzer, B., Ludwig, S., Rapp, U. R. (2005). MAPKAP Kinase 3pK Phosphorylates and Regulates Chromatin Association of the Polycomb Group Protein Bmi1. J. Biol. Chem. 280: 5178-5187 [Abstract] [Full Text]  
  • Roux, P. P., Blenis, J. (2004). ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions. Microbiol. Mol. Biol. Rev. 68: 320-344 [Abstract] [Full Text]  
  • Ikuta, T., Kobayashi, Y., Kawajiri, K. (2004). Cell Density Regulates Intracellular Localization of Aryl Hydrocarbon Receptor. J. Biol. Chem. 279: 19209-19216 [Abstract] [Full Text]  
  • Lui, P., Zeng, C., Acton, S., Cok, S., Sexton, A., Morrison, A. R. (2004). Effects of p38MAPK isoforms on renal mesangial cell inducible nitric oxide synthase expression. Am. J. Physiol. Cell Physiol. 286: C145-C152 [Abstract] [Full Text]  
  • Shi, Y., Kotlyarov, A., Laass, K., Gruber, A. D., Butt, E., Marcus, K., Meyer, H. E., Friedrich, A., Volk, H.-D., Gaestel, M. (2003). Elimination of Protein Kinase MK5/PRAK Activity by Targeted Homologous Recombination. Mol. Cell. Biol. 23: 7732-7741 [Abstract] [Full Text]  
  • Scheper, G. C., Parra, J. L., Wilson, M., van Kollenburg, B., Vertegaal, A. C. O., Han, Z.-G., Proud, C. G. (2003). The N and C Termini of the Splice Variants of the Human Mitogen-Activated Protein Kinase-Interacting Kinase Mnk2 Determine Activity and Localization. Mol. Cell. Biol. 23: 5692-5705 [Abstract] [Full Text]  
  • New, L., Jiang, Y., Han, J. (2003). Regulation of PRAK Subcellular Location by p38 MAP Kinases. Mol. Biol. Cell 14: 2603-2616 [Abstract] [Full Text]  
  • Qiu, M., Olsen, A., Faivre, E., Horwitz, K. B., Lange, C. A. (2003). Mitogen-Activated Protein Kinase Regulates Nuclear Association of Human Progesterone Receptors. Mol. Endocrinol. 17: 628-642 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»