The unique C-terminal tail of the mitogen-activated protein kinase ERK5 regulates its activation and nuclear shuttling

doi:10.1074/jbc.M412599200

HOME

HELP

FEEDBACK

SUBSCRIPTIONS

The unique C-terminal tail of the mitogen-activated protein kinase ERK5 regulates its activation and nuclear shuttling

Marcus Buschbeck and Axel Ullrich

Cancer and Differentiation, Center for Genomic Regulation, Barcelona 08003

Corresponding Author: marcus.buschbeck{at}crg.es

ERK5 is unique among mitogen-activated protein kinases (MAPKs) in that it contains a large C-terminal tail. We addressed the question how this tail could affect the signaling capacity of ERK5. Gradual deletion of the C-terminal domains resulted in a drastic increase of ERK5 kinase activity, which was dependent on the upstream MAPK cascade thus indicating a possible auto-inhibitory function of the tail. Interestingly, ERK5 was able to auto-phosphorylate its own tail. Moreover ERK5, which was found to be expressed in virtually all kinds of cell lines, localized to nuclear as well as cytoplasmic compartments. The localization of ERK5 was determined by its C-terminal domains, which were also required for appropriate nucleo-cytoplasmic shuttling. Taken together these results indicate that ERK5 signaling is directed by the presence of its unique C-terminal tail, which might be the key to understand the outstanding role of ERK5 in MAPK signaling.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

T. T. C. Yang, R. Y. L. Yu, A. Agadir, G.-J. Gao, R. Campos-Gonzalez, C. Tournier, and C.-W. Chow
Integration of Protein Kinases mTOR and Extracellular Signal-Regulated Kinase 5 in Regulating Nucleocytoplasmic Localization of NFATc4
Mol. Cell. Biol., May 15, 2008; 28(10): 3489 - 3501.
[Abstract] [Full Text] [PDF]

H. Morimoto, K. Kondoh, S. Nishimoto, K. Terasawa, and E. Nishida
Activation of a C-terminal Transcriptional Activation Domain of ERK5 by Autophosphorylation
J. Biol. Chem., December 7, 2007; 282(49): 35449 - 35456.
[Abstract] [Full Text] [PDF]

A. L. Mundy, E. Haas, I. Bhattacharya, C. C. Widmer, M. Kretz, R. Hofmann-Lehmann, R. Minotti, and M. Barton
Fat intake modifies vascular responsiveness and receptor expression of vasoconstrictors: Implications for diet-induced obesity
Cardiovasc Res, January 15, 2007; 73(2): 368 - 375.
[Abstract] [Full Text] [PDF]

J. Garaude, S. Cherni, S. Kaminski, E. Delepine, C. Chable-Bessia, M. Benkirane, J. Borges, A. Pandiella, M. A. Iniguez, M. Fresno, et al.
ERK5 Activates NF-{kappa}B in Leukemic T Cells and Is Essential for Their Growth In Vivo
J. Immunol., December 1, 2006; 177(11): 7607 - 7617.
[Abstract] [Full Text] [PDF]

A. W. Truman, S. H. Millson, J. M. Nuttall, V. King, M. Mollapour, C. Prodromou, L. H. Pearl, and P. W. Piper
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, November 1, 2006; 5(11): 1914 - 1924.
[Abstract] [Full Text] [PDF]

C. Iavarone, M. Acunzo, F. Carlomagno, A. Catania, R. M. Melillo, S. M. Carlomagno, M. Santoro, and M. Chiariello
Activation of the Erk8 Mitogen-activated Protein (MAP) Kinase by RET/PTC3, a Constitutively Active Form of the RET Proto-oncogene
J. Biol. Chem., April 14, 2006; 281(15): 10567 - 10576.
[Abstract] [Full Text] [PDF]

J. Seyfried, X. Wang, G. Kharebava, and C. Tournier
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., November 15, 2005; 25(22): 9820 - 9828.
[Abstract] [Full Text] [PDF]

All ASBMB Journals	Molecular and Cellular Proteomics
Journal of Lipid Research	ASBMB Today

				H. Morimoto, K. Kondoh, S. Nishimoto, K. Terasawa, and E. Nishida Activation of a C-terminal Transcriptional Activation Domain of ERK5 by Autophosphorylation J. Biol. Chem., December 7, 2007; 282(49): 35449 - 35456. [Abstract] [Full Text] [PDF]

				A. L. Mundy, E. Haas, I. Bhattacharya, C. C. Widmer, M. Kretz, R. Hofmann-Lehmann, R. Minotti, and M. Barton Fat intake modifies vascular responsiveness and receptor expression of vasoconstrictors: Implications for diet-induced obesity Cardiovasc Res, January 15, 2007; 73(2): 368 - 375. [Abstract] [Full Text] [PDF]

				J. Garaude, S. Cherni, S. Kaminski, E. Delepine, C. Chable-Bessia, M. Benkirane, J. Borges, A. Pandiella, M. A. Iniguez, M. Fresno, et al. ERK5 Activates NF-{kappa}B in Leukemic T Cells and Is Essential for Their Growth In Vivo J. Immunol., December 1, 2006; 177(11): 7607 - 7617. [Abstract] [Full Text] [PDF]

				A. W. Truman, S. H. Millson, J. M. Nuttall, V. King, M. Mollapour, C. Prodromou, L. H. Pearl, and P. W. Piper 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, November 1, 2006; 5(11): 1914 - 1924. [Abstract] [Full Text] [PDF]

				C. Iavarone, M. Acunzo, F. Carlomagno, A. Catania, R. M. Melillo, S. M. Carlomagno, M. Santoro, and M. Chiariello Activation of the Erk8 Mitogen-activated Protein (MAP) Kinase by RET/PTC3, a Constitutively Active Form of the RET Proto-oncogene J. Biol. Chem., April 14, 2006; 281(15): 10567 - 10576. [Abstract] [Full Text] [PDF]

				J. Seyfried, X. Wang, G. Kharebava, and C. Tournier 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., November 15, 2005; 25(22): 9820 - 9828. [Abstract] [Full Text] [PDF]