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 Kasler, H. G.
Right arrow Articles by Winoto, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kasler, H. G.
Right arrow Articles by Winoto, A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2000, p. 8382-8389, Vol. 20, No. 22
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

ERK5 Is a Novel Type of Mitogen-Activated Protein Kinase Containing a Transcriptional Activation Domain

Herbert G. Kasler, Joseph Victoria, Omar Duramad, and Astar Winoto*

Cancer Research Lab and Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200

Received 21 June 2000/Returned for modification 2 August 2000/Accepted 15 August 2000

Previous studies have shown that upregulation of the orphan steroid receptor Nur77 is required for the apoptosis of immature T cells in response to antigen receptor signals. Transcriptional upregulation of Nur77 in response to antigen receptor signaling involves two binding sites for the MEF2 family of transcription factors located in the Nur77 promoter. Calcium signals greatly increase the activity of MEF2D in T cells via a posttranslational mechanism. The mitogen-activated protein (MAP) kinase ERK5 was isolated in a yeast two-hybrid screen using the MADS-MEF2 domain of MEF2D as bait. ERK5 resembles the other MAP kinase family members in its N-terminal half, but it also contains a 400-amino-acid C-terminal domain of previously uncharacterized function. We report here that the C-terminal region of ERK5 contains a MEF2-interacting domain and, surprisingly, also a potent transcriptional activation domain. These domains are both required for coactivation of MEF2D by ERK5. The MEF2-ERK5 interaction was found to be activation dependent in vivo and inhibitable in vitro by the calcium-sensitive MEF2 repressor Cabin 1. The transcriptional activation domain of ERK5 is required for maximal MEF2 activity in response to calcium flux in T cells, and it can activate the endogenous Nur77 gene when constitutively recruited to the Nur77 promoter via MEF2 sites. These studies provide insights into a mechanism whereby MEF2 activity can respond to calcium signaling and suggest a novel, unexpected mechanism of MAP kinase function.

* Corresponding author. Mailing address: Department of Molecular and Cell Biology, Cancer Research Lab and Division of Immunology, 469 LSA, University of California, Berkeley, CA 94720-3200. Phone: (510) 642-0217. Fax: (510) 642-0468. E-mail: winoto{at}uclink4.berkeley.edu.

Molecular and Cellular Biology, November 2000, p. 8382-8389, Vol. 20, No. 22
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Spiering, D., Schmolke, M., Ohnesorge, N., Schmidt, M., Goebeler, M., Wegener, J., Wixler, V., Ludwig, S. (2009). MEK5/ERK5 Signaling Modulates Endothelial Cell Migration and Focal Contact Turnover. J. Biol. Chem. 284: 24972-24980 [Abstract] [Full Text]  
  • Carter, E. J., Cosgrove, R. A., Gonzalez, I., Eisemann, J. H., Lovett, F. A., Cobb, L. J., Pell, J. M. (2009). MEK5 and ERK5 are mediators of the pro-myogenic actions of IGF-2. J. Cell Sci. 122: 3104-3112 [Abstract] [Full Text]  
  • Pazyra-Murphy, M. F., Hans, A., Courchesne, S. L., Karch, C., Cosker, K. E., Heerssen, H. M., Watson, F. L., Kim, T., Greenberg, M. E., Segal, R. A. (2009). A Retrograde Neuronal Survival Response: Target-Derived Neurotrophins Regulate MEF2D and bcl-w. J. Neurosci. 29: 6700-6709 [Abstract] [Full Text]  
  • Dorado, F., Velasco, S., Esparis-Ogando, A., Pericacho, M., Pandiella, A., Silva, J., Lopez-Novoa, J. M., Rodriguez-Barbero, A. (2008). The mitogen-activated protein kinase Erk5 mediates human mesangial cell activation. Nephrol Dial Transplant 23: 3403-3411 [Abstract] [Full Text]  
  • Schramp, M., Ying, O., Kim, T. Y., Martin, G. S. (2008). ERK5 promotes Src-induced podosome formation by limiting Rho activation. JCB 181: 1195-1210 [Abstract] [Full Text]  
  • Thompson, J., Winoto, A. (2008). During negative selection, Nur77 family proteins translocate to mitochondria where they associate with Bcl-2 and expose its proapoptotic BH3 domain. JEM 205: 1029-1036 [Abstract] [Full Text]  
  • Fujii, Y., Matsuda, S., Takayama, G., Koyasu, S. (2008). ERK5 is involved in TCR-induced apoptosis through the modification of Nur77.. GENES CELLS 13: 411-419 [Abstract] [Full Text]  
  • Woo, C.-H., Shishido, T., McClain, C., Lim, J. H., Li, J.-D., Yang, J., Yan, C., Abe, J.-i. (2008). Extracellular Signal-Regulated Kinase 5 SUMOylation Antagonizes Shear Stress-Induced Antiinflammatory Response and Endothelial Nitric Oxide Synthase Expression in Endothelial Cells. Circ. Res. 102: 538-545 [Abstract] [Full Text]  
  • Xue, L., Nolla, H., Suzuki, A., Mak, T. W., Winoto, A. (2008). Normal development is an integral part of tumorigenesis in T cell-specific PTEN-deficient mice. Proc. Natl. Acad. Sci. USA 105: 2022-2027 [Abstract] [Full Text]  
  • Morimoto, H., Kondoh, K., Nishimoto, S., Terasawa, K., Nishida, E. (2007). Activation of a C-terminal Transcriptional Activation Domain of ERK5 by Autophosphorylation. J. Biol. Chem. 282: 35449-35456 [Abstract] [Full Text]  
  • Kasler, H. G., Verdin, E. (2007). Histone Deacetylase 7 Functions as a Key Regulator of Genes Involved in both Positive and Negative Selection of Thymocytes. Mol. Cell. Biol. 27: 5184-5200 [Abstract] [Full Text]  
  • Yan, C., Ding, B., Shishido, T., Woo, C.-H., Itoh, S., Jeon, K.-I., Liu, W., Xu, H., McClain, C., Molina, C. A., Blaxall, B. C., Abe, J.-i. (2007). Activation of Extracellular Signal-Regulated Kinase 5 Reduces Cardiac Apoptosis and Dysfunction via Inhibition of a Phosphodiesterase 3A/Inducible cAMP Early Repressor Feedback Loop. Circ. Res. 100: 510-519 [Abstract] [Full Text]  
  • Gregoire, S., Xiao, L., Nie, J., Zhang, X., Xu, M., Li, J., Wong, J., Seto, E., Yang, X.-J. (2007). Histone Deacetylase 3 Interacts with and Deacetylates Myocyte Enhancer Factor 2. Mol. Cell. Biol. 27: 1280-1295 [Abstract] [Full Text]  
  • Garaude, J., Cherni, S., Kaminski, S., Delepine, E., Chable-Bessia, C., Benkirane, M., Borges, J., Pandiella, A., Iniguez, M. A., Fresno, M., Hipskind, R. A., Villalba, M. (2006). ERK5 Activates NF-{kappa}B in Leukemic T Cells and Is Essential for Their Growth In Vivo. J. Immunol. 177: 7607-7617 [Abstract] [Full Text]  
  • Truman, A. W., Millson, S. H., Nuttall, J. M., King, V., Mollapour, M., Prodromou, C., Pearl, L. H., Piper, P. W. (2006). Expressed in the Yeast Saccharomyces cerevisiae, Human ERK5 Is a Client of the Hsp90 Chaperone That Complements Loss of the Slt2p (Mpk1p) Cell Integrity Stress-Activated Protein Kinase. Eukaryot Cell 5: 1914-1924 [Abstract] [Full Text]  
  • Woo, C.-H., Massett, M. P., Shishido, T., Itoh, S., Ding, B., McClain, C., Che, W., Vulapalli, S. R., Yan, C., Abe, J.-i. (2006). ERK5 Activation Inhibits Inflammatory Responses via Peroxisome Proliferator-activated Receptor {delta} (PPAR{delta}) Stimulation. J. Biol. Chem. 281: 32164-32174 [Abstract] [Full Text]  
  • Schweppe, R. E., Cheung, T. H., Ahn, N. G. (2006). Global Gene Expression Analysis of ERK5 and ERK1/2 Signaling Reveals a Role for HIF-1 in ERK5-mediated Responses. J. Biol. Chem. 281: 20993-21003 [Abstract] [Full Text]  
  • Kondoh, K., Terasawa, K., Morimoto, H., Nishida, E. (2006). Regulation of nuclear translocation of extracellular signal-regulated kinase 5 by active nuclear import and export mechanisms.. Mol. Cell. Biol. 26: 1679-1690 [Abstract] [Full Text]  
  • Gregoire, S., Tremblay, A. M., Xiao, L., Yang, Q., Ma, K., Nie, J., Mao, Z., Wu, Z., Giguere, V., Yang, X.-J. (2006). Control of MEF2 Transcriptional Activity by Coordinated Phosphorylation and Sumoylation. J. Biol. Chem. 281: 4423-4433 [Abstract] [Full Text]  
  • Seyfried, J., Wang, X., Kharebava, G., Tournier, C. (2005). A Novel Mitogen-Activated Protein Kinase Docking Site in the N Terminus of MEK5{alpha} Organizes the Components of the Extracellular Signal-Regulated Kinase 5 Signaling Pathway. Mol. Cell. Biol. 25: 9820-9828 [Abstract] [Full Text]  
  • Sohn, S. J., Li, D., Lee, L. K., Winoto, A. (2005). Transcriptional Regulation of Tissue-Specific Genes by the ERK5 Mitogen-Activated Protein Kinase. Mol. Cell. Biol. 25: 8553-8566 [Abstract] [Full Text]  
  • Nakagawa, O., Arnold, M., Nakagawa, M., Hamada, H., Shelton, J. M., Kusano, H., Harris, T. M., Childs, G., Campbell, K. P., Richardson, J. A., Nishino, I., Olson, E. N. (2005). Centronuclear myopathy in mice lacking a novel muscle-specific protein kinase transcriptionally regulated by MEF2. Genes Dev. 19: 2066-2077 [Abstract] [Full Text]  
  • Fu, Z., Schroeder, M. J., Shabanowitz, J., Kaldis, P., Togawa, K., Rustgi, A. K., Hunt, D. F., Sturgill, T. W. (2005). Activation of a Nuclear Cdc2-Related Kinase within a Mitogen-Activated Protein Kinase-Like TDY Motif by Autophosphorylation and Cyclin-Dependent Protein Kinase-Activating Kinase. Mol. Cell. Biol. 25: 6047-6064 [Abstract] [Full Text]  
  • Sturla, L.-M., Cowan, C. W., Guenther, L., Castellino, R. C., Kim, J. Y.H., Pomeroy, S. L. (2005). A Novel Role for Extracellular Signal-Regulated Kinase 5 and Myocyte Enhancer Factor 2 in Medulloblastoma Cell Death. Cancer Res. 65: 5683-5689 [Abstract] [Full Text]  
  • Carvajal-Vergara, X., Tabera, S., Montero, J. C., Esparis-Ogando, A., Lopez-Perez, R., Mateo, G., Gutierrez, N., Parmo-Cabanas, M., Teixido, J., San Miguel, J. F., Pandiella, A. (2005). Multifunctional role of Erk5 in multiple myeloma. Blood 105: 4492-4499 [Abstract] [Full Text]  
  • Millson, S. H., Truman, A. W., King, V., Prodromou, C., Pearl, L. H., Piper, P. W. (2005). A Two-Hybrid Screen of the Yeast Proteome for Hsp90 Interactors Uncovers a Novel Hsp90 Chaperone Requirement in the Activity of a Stress-Activated Mitogen-Activated Protein Kinase, Slt2p (Mpk1p). Eukaryot Cell 4: 849-860 [Abstract] [Full Text]  
  • Barros, J. C., Marshall, C. J. (2005). Activation of either ERK1/2 or ERK5 MAP kinase pathways can lead to disruption of the actin cytoskeleton. J. Cell Sci. 118: 1663-1671 [Abstract] [Full Text]  
  • Parra, M., Kasler, H., McKinsey, T. A., Olson, E. N., Verdin, E. (2005). Protein Kinase D1 Phosphorylates HDAC7 and Induces Its Nuclear Export after T-cell Receptor Activation. J. Biol. Chem. 280: 13762-13770 [Abstract] [Full Text]  
  • Gregoire, S., Yang, X.-J. (2005). Association with Class IIa Histone Deacetylases Upregulates the Sumoylation of MEF2 Transcription Factors. Mol. Cell. Biol. 25: 2273-2287 [Abstract] [Full Text]  
  • Dequiedt, F., Van Lint, J., Lecomte, E., Van Duppen, V., Seufferlein, T., Vandenheede, J. R., Wattiez, R., Kettmann, R. (2005). Phosphorylation of histone deacetylase 7 by protein kinase D mediates T cell receptor-induced Nur77 expression and apoptosis. JEM 201: 793-804 [Abstract] [Full Text]  
  • Carrasco, J. L., Ancillo, G., Castello, M. J., Vera, P. (2005). A Novel DNA-Binding Motif, Hallmark of a New Family of Plant Transcription Factors. Plant Physiol. 137: 602-606 [Full Text]  
  • Buschbeck, M., Ullrich, A. (2005). The Unique C-terminal Tail of the Mitogen-activated Protein Kinase ERK5 Regulates Its Activation and Nuclear Shuttling. J. Biol. Chem. 280: 2659-2667 [Abstract] [Full Text]  
  • Wang, X., Merritt, A. J., Seyfried, J., Guo, C., Papadakis, E. S., Finegan, K. G., Kayahara, M., Dixon, J., Boot-Handford, R. P., Cartwright, E. J., Mayer, U., Tournier, C. (2005). Targeted Deletion of mek5 Causes Early Embryonic Death and Defects in the Extracellular Signal-Regulated Kinase 5/Myocyte Enhancer Factor 2 Cell Survival Pathway. Mol. Cell. Biol. 25: 336-345 [Abstract] [Full Text]  
  • Akaike, M., Che, W., Marmarosh, N.-L., Ohta, S., Osawa, M., Ding, B., Berk, B. C., Yan, C., Abe, J.-i. (2004). The Hinge-Helix 1 Region of Peroxisome Proliferator-Activated Receptor {gamma}1 (PPAR{gamma}1) Mediates Interaction with Extracellular Signal-Regulated Kinase 5 and PPAR{gamma}1 Transcriptional Activation: Involvement in Flow-Induced PPAR{gamma} Activation in Endothelial Cells. Mol. Cell. Biol. 24: 8691-8704 [Abstract] [Full Text]  
  • Edmunds, J. W., Mahadevan, L. C. (2004). MAP kinases as structural adaptors and enzymatic activators in transcription complexes. J. Cell Sci. 117: 3715-3723 [Abstract] [Full Text]  
  • Kuida, K., Boucher, D. M. (2004). Functions of MAP Kinases: Insights from Gene-Targeting Studies. J Biochem 135: 653-656 [Abstract] [Full Text]  
  • Kuo, W.-L., Duke, C. J., Abe, M. K., Kaplan, E. L., Gomes, S., Rosner, M. R. (2004). ERK7 Expression and Kinase Activity Is Regulated by the Ubiquitin-Proteosome Pathway. J. Biol. Chem. 279: 23073-23081 [Abstract] [Full Text]  
  • Raviv, Z., Kalie, E., Seger, R. (2004). MEK5 and ERK5 are localized in the nuclei of resting as well as stimulated cells, while MEKK2 translocates from the cytosol to the nucleus upon stimulation. J. Cell Sci. 117: 1773-1784 [Abstract] [Full Text]  
  • Zheng, Q., Yin, G., Yan, C., Cavet, M., Berk, B. C. (2004). 14-3-3{beta} Binds to Big Mitogen-activated Protein Kinase 1 (BMK1/ERK5) and Regulates BMK1 Function. J. Biol. Chem. 279: 8787-8791 [Abstract] [Full Text]  
  • Cameron, S. J., Abe, J.-i., Malik, S., Che, W., Yang, J. (2004). Differential Role of MEK5{alpha} and MEK5{beta} in BMK1/ERK5 Activation. J. Biol. Chem. 279: 1506-1512 [Abstract] [Full Text]  
  • Cameron, S. J., Malik, S., Akaike, M., Lerner-Marmarosh, N., Yan, C., Lee, J.-D., Abe, J.-i., Yang, J. (2003). Regulation of Epidermal Growth Factor-induced Connexin 43 Gap Junction Communication by Big Mitogen-activated Protein Kinase 1/ERK5 but Not ERK1/2 Kinase Activation. J. Biol. Chem. 278: 18682-18688 [Abstract] [Full Text]  
  • Gupta, P., Prywes, R. (2002). ATF1 Phosphorylation by the ERK MAPK Pathway Is Required for Epidermal Growth Factor-induced c-jun Expression. J. Biol. Chem. 277: 50550-50556 [Abstract] [Full Text]  
  • Sohn, S. J., Sarvis, B. K., Cado, D., Winoto, A. (2002). ERK5 MAPK Regulates Embryonic Angiogenesis and Acts as a Hypoxia-sensitive Repressor of Vascular Endothelial Growth Factor Expression. J. Biol. Chem. 277: 43344-43351 [Abstract] [Full Text]  
  • Dwivedi, P. P., Hii, C. S. T., Ferrante, A., Tan, J., Der, C. J., Omdahl, J. L., Morris, H. A., May, B. K. (2002). Role of MAP Kinases in the 1,25-Dihydroxyvitamin D3-induced Transactivation of the Rat Cytochrome P450C24 (CYP24) Promoter. SPECIFIC FUNCTIONS FOR ERK1/ERK2 AND ERK5. J. Biol. Chem. 277: 29643-29653 [Abstract] [Full Text]  
  • Regan, C. P., Li, W., Boucher, D. M., Spatz, S., Su, M. S., Kuida, K. (2002). Erk5 null mice display multiple extraembryonic vascular and embryonic cardiovascular defects. Proc. Natl. Acad. Sci. USA 99: 9248-9253 [Abstract] [Full Text]  
  • Reddy, S. P. M., Adiseshaiah, P., Shapiro, P., Vuong, H. (2002). BMK1 (ERK5) Regulates Squamous Differentiation Marker SPRR1B Transcription in Clara-like H441 Cells. Am. J. Respir. Cell Mol. Bio. 27: 64-70 [Abstract] [Full Text]  
  • Abe, M. K., Saelzler, M. P., Espinosa, R. III, Kahle, K. T., Hershenson, M. B., Le Beau, M. M., Rosner, M. R. (2002). ERK8, a New Member of the Mitogen-activated Protein Kinase Family. J. Biol. Chem. 277: 16733-16743 [Abstract] [Full Text]  
  • Janulis, M., Trakul, N., Greene, G., Schaefer, E. M., Lee, J. D., Rosner, M. R. (2001). A Novel Mitogen-Activated Protein Kinase Is Responsive to Raf and Mediates Growth Factor Specificity. Mol. Cell. Biol. 21: 2235-2247 [Abstract] [Full Text]  
  • Dong, F., Gutkind, J. S., Larner, A. C. (2001). Granulocyte Colony-stimulating Factor Induces Erk5 Activation, Which Is Differentially Regulated by Protein-tyrosine Kinases and Protein Kinase C. REGULATION OF CELL PROLIFERATION AND SURVIVAL. J. Biol. Chem. 276: 10811-10816 [Abstract] [Full Text]  
  • Kumar, N. V., Bernstein, L. R. (2001). Ten ERK-related Proteins in Three Distinct Classes Associate with AP-1 Proteins and/or AP-1 DNA. J. Biol. Chem. 276: 32362-32372 [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»