MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen- activated protein kinase signal transduction pathway

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Mol. Cell. Biol., 03 1996, 1247-1255, Vol 16, No. 3
Copyright © 1996, American Society for Microbiology

MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen- activated protein kinase signal transduction pathway

J Raingeaud, AJ Whitmarsh, T Barrett, B Derijard and RJ Davis
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester 01605 USA.

The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway.

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Park, J. S., Svetkauskaite, D., He, Q., Kim, J.-Y., Strassheim, D., Ishizaka, A., Abraham, E. (2004). Involvement of Toll-like Receptors 2 and 4 in Cellular Activation by High Mobility Group Box 1 Protein. J. Biol. Chem. 279: 7370-7377 [Abstract] [Full Text]
Stambe, C., Nikolic-Paterson, D. J., Hill, P. A., Dowling, J., Atkins, R. C. (2004). p38 Mitogen-Activated Protein Kinase Activation and Cell Localization in Human Glomerulonephritis: Correlation with Renal Injury. J. Am. Soc. Nephrol. 15: 326-336 [Abstract] [Full Text]
Ho, R. C., Alcazar, O., Fujii, N., Hirshman, M. F., Goodyear, L. J. (2004). p38{gamma} MAPK regulation of glucose transporter expression and glucose uptake in L6 myotubes and mouse skeletal muscle. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286: R342-R349 [Abstract] [Full Text]
Sanders, P. W. (2004). Salt Intake, Endothelial Cell Signaling, and Progression of Kidney Disease. Hypertension 43: 142-146 [Abstract] [Full Text]
Shibazaki, M., Takeuchi, T., Ahmed, S., Kikuchi, H. (2004). Suppression by p38 MAP Kinase Inhibitors (Pyridinyl Imidazole Compounds) of Ah Receptor Target Gene Activation by 2,3,7,8-Tetrachlorodibenzo-p-dioxin and the Possible Mechanism. J. Biol. Chem. 279: 3869-3876 [Abstract] [Full Text]
Inoue, K., Zama, T., Kamimoto, T., Aoki, R., Ikeda, Y., Kimura, H., Hagiwara, M. (2004). TNF{alpha}-induced ATF3 expression is bidirectionally regulated by the JNK and ERK pathways in vascular endothelial cells. GENES CELLS 9: 59-70 [Abstract] [Full Text]
Chabaud-Riou, M., Firestein, G. S. (2004). Expression and Activation of Mitogen-Activated Protein Kinase Kinases-3 and -6 in Rheumatoid Arthritis. Am. J. Pathol. 164: 177-184 [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]
Xiu, M., Kim, J., Sampson, E., Huang, C.-Y., Davis, R. J., Paulson, K. E., Yee, A. S. (2003). The Transcriptional Repressor HBP1 Is a Target of the p38 Mitogen-Activated Protein Kinase Pathway in Cell Cycle Regulation. Mol. Cell. Biol. 23: 8890-8901 [Abstract] [Full Text]
Otterbein, L. E., Otterbein, S. L., Ifedigbo, E., Liu, F., Morse, D. E., Fearns, C., Ulevitch, R. J., Knickelbein, R., Flavell, R. A., Choi, A. M. (2003). MKK3 Mitogen-Activated Protein Kinase Pathway Mediates Carbon Monoxide-Induced Protection Against Oxidant-Induced Lung Injury. Am. J. Pathol. 163: 2555-2563 [Abstract] [Full Text]
Lee, T. H., Huang, Q., Oikemus, S., Shank, J., Ventura, J.-J., Cusson, N., Vaillancourt, R. R., Su, B., Davis, R. J., Kelliher, M. A. (2003). The Death Domain Kinase RIP1 Is Essential for Tumor Necrosis Factor Alpha Signaling to p38 Mitogen-Activated Protein Kinase. Mol. Cell. Biol. 23: 8377-8385 [Abstract] [Full Text]

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