BACKGROUND: ERK5 is the newest subfamily member of the mitogen-activated protein kinase (MAPK) family, and is activated by various extracellular signals including growth factors. MEK5 is a specific activator of ERK5. c-Fos and Fra-1, well-known immediate early gene products, are members of the AP-1 family. We previously reported that activation of the MEK5-ERK5 pathway is able to induce expression of c-Fos. RESULTS: We have found that activation of the MEK5-ERK5 pathway causes the phosphorylation and stabilization of c-Fos and Fra-1. Phosphorylation of c-Fos appears to be mediated by ERK5 and a kinase(s) lying downstream of ERK5, and the MEK5-ERK5 pathway-dependent phosphorylation sites on c-Fos are different from the ERK1/2 pathway-dependent ones. Interestingly, activation of the MEK5-ERK5 pathway, but not that of the ERK1/2 pathway, is found to markedly increase the transactivation activity of c-Fos. Furthermore, our results show that the C-terminal half of ERK5 is necessary for the maximal activation of the transactivation activity of c-Fos and Fra-1. CONCLUSION: These results reveal a role of the MEK5-ERK5 pathway in modulating the function of the Fos family proteins which is different from the role of the ERK1/2 pathway.

This article has been cited by other articles:

				M. E. Ramos-Nino, S. R. Blumen, T. Sabo-Attwood, H. Pass, M. Carbone, J. R. Testa, D. A. Altomare, and B. T. Mossman HGF Mediates Cell Proliferation of Human Mesothelioma Cells through a PI3K/MEK5/Fra-1 Pathway Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 209 - 217. [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]

				J. Basbous, D. Chalbos, R. Hipskind, I. Jariel-Encontre, and M. Piechaczyk Ubiquitin-Independent Proteasomal Degradation of Fra-1 Is Antagonized by Erk1/2 Pathway-Mediated Phosphorylation of a Unique C-Terminal Destabilizer Mol. Cell. Biol., June 1, 2007; 27(11): 3936 - 3950. [Abstract] [Full Text] [PDF]

				R. Natrajan, S. E. Little, J. S. Reis-Filho, L. Hing, B. Messahel, P. E. Grundy, J. S. Dome, T. Schneider, G. M. Vujanic, K. Pritchard-Jones, et al. Amplification and Overexpression of CACNA1E Correlates with Relapse in Favorable Histology Wilms' Tumors Clin. Cancer Res., December 15, 2006; 12(24): 7284 - 7293. [Abstract] [Full Text] [PDF]

				K. Kondoh, K. Terasawa, H. Morimoto, and E. Nishida Regulation of nuclear translocation of extracellular signal-regulated kinase 5 by active nuclear import and export mechanisms. Mol. Cell. Biol., March 1, 2006; 26(5): 1679 - 1690. [Abstract] [Full Text] [PDF]

				G. Bossis, C. E. Malnou, R. Farras, E. Andermarcher, R. Hipskind, M. Rodriguez, D. Schmidt, S. Muller, I. Jariel-Encontre, and M. Piechaczyk Down-Regulation of c-Fos/c-Jun AP-1 Dimer Activity by Sumoylation Mol. Cell. Biol., August 15, 2005; 25(16): 6964 - 6979. [Abstract] [Full Text] [PDF]

				T. Tanos, M. J. Marinissen, F. C. Leskow, D. Hochbaum, H. Martinetto, J. S. Gutkind, and O. A. Coso Phosphorylation of c-Fos by Members of the p38 MAPK Family: ROLE IN THE AP-1 RESPONSE TO UV LIGHT J. Biol. Chem., May 13, 2005; 280(19): 18842 - 18852. [Abstract] [Full Text] [PDF]

				E. Hoffmann, A. Thiefes, D. Buhrow, O. Dittrich-Breiholz, H. Schneider, K. Resch, and M. Kracht MEK1-dependent Delayed Expression of Fos-related Antigen-1 Counteracts c-Fos and p65 NF-{kappa}B-mediated Interleukin-8 Transcription in Response to Cytokines or Growth Factors J. Biol. Chem., March 11, 2005; 280(10): 9706 - 9718. [Abstract] [Full Text] [PDF]

				X. Wang, A. J. Merritt, J. Seyfried, C. Guo, E. S. Papadakis, K. G. Finegan, M. Kayahara, J. Dixon, R. P. Boot-Handford, E. J. Cartwright, et al. 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., January 1, 2005; 25(1): 336 - 345. [Abstract] [Full Text] [PDF]

				Z. Raviv, E. Kalie, and R. Seger 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., May 1, 2004; 117(9): 1773 - 1784. [Abstract] [Full Text] [PDF]

				N. Higashi, H. Kunimoto, S. Kaneko, T. Sasaki, M. Ishii, H. Kojima, and K. Nakajima Cytoplasmic c-Fos induced by the YXXQ-derived STAT3 signal requires the co-operative MEK/ERK signal for its nuclear translocation Genes Cells, March 1, 2004; 9(3): 233 - 242. [Abstract] [Full Text] [PDF]