Abstract
THE stress-activated protein kinases (SAPKs), which are distantly related to the MAP kinases, are the dominant c-Jun amino-termi-nal protein kinases activated in response to a variety of cellular stresses, including treatment with tumour-necrosis factor-α and interleukin-β (refs 1, 2). SAPK phosphorylation of c-Jun probably activates the c-Jun transactivation function3. SAPKs are part of a signal transduction cascade related to, but distinct from, the MAPK pathway1. We have now identified a novel protein kinase, called SAPK/ERK kinase-1 (SEK1), which is structurally related to the MAP kinase kinases (MEKs)4. SEK1 is a potent activator of the SAPKs in vitro and in vivo. An inactive SEK1 mutant blocks SAPK activation by extracellular stimuli without interfering with the MAPK pathway. Although alternative mechanisms of SAPK activation may exist, as an immediate upstream activator of the SAPKs, SEK1 further defines a signalling cascade that couples cellular stress agonists to the c-Jun transcription factor.
Similar content being viewed by others
Article PDF
References
Kyriakis, J. M. et al. Nature 369, 156–160 (1994).
Dérijard, B. et al. Cell 76, 1025–1037 (1994).
Pulverer, B. J. et al. Nature 353, 670–674 (1991).
Crews, C. M., Alessandrini, A. & Erikson, R. L. Science 258, 478–480 (1992).
Yashar, B. M. et al. Molec. cell. Biol. 13, 5738–5748 (1993).
Ahn, N. G., Seger, R. & Krebs, E. G. Curr. Opin. Cell Biol. 4, 992–999 (1992).
Hanks, S. K., Quinn, A. M. & Hunter, T. Science 241, 42–52 (1988).
Zheng, C.-F. & Guan, K.-L. EMBO J. 13, 1123–1131 (1994).
Alessi, D. R. et al. EMBO J. 13, 1610–1619 (1994).
Yan, M. & Templeton, D. J. J. biol. Chem. 269, 19067–19073 (1994).
Nakieiny, S., Cohen, P., Wu, J. & Sturgill, T. W. EMBO J. 11, 2123–2129 (1992).
Kyriakis, J. M., Brautigan, D. L., Ingebritsen, T. S. & Avruch, J. J. biol. Chem. 266, 10043–10046 (1991).
Mukhopadhyay, N. K. et al. J. biol. Chem. 267, 3325–3335 (1992).
Her, J.-H. et al. Biochem. J. 296, 25–31 (1993).
Leevers, S. J. & Marshall, C. J. EMBO J. 11, 569–574 (1992).
Wood, K. W., Sarnecki, C., Roberts, T. M. & Blenis, J. Cell 68, 1041–1050 (1992).
Han, J., Lee, J.-D., Bibbs, L. & Ulevitch, R. J. Science 265, 808–811 (1994).
Rouse, J. et al. Cell 78, 1027–1037 (1994).
Freshney, N. W. et al. Cell 78, 1039–1049 (1994).
Yan, M. et al. Nature, 372, 788–800 (1994).
Lange-Carter, C. A. et al. Science 260, 315–319 (1993).
Blumer, K. J. & Johnson, G. L. Trends biochem. Sci. 19, 236–240 (1994).
Grove, J. R. et al. Molec. cell. Biol. 11, 5541–5550 (1991).
Mizushima, S. & Nagata, S. Nucleic Acids Res. 18, 5322 (1990).
Ho, S. N. et al. Gene 77, 51–59 (1989).
Smith, D. B. & Johnson, D. S. Gene 67, 31–40 (1988).
Boyle, W. J., van der Geer, T. & Hunter, T. Meth. Enzym. 201, 110–152 (1991).
Aruffo, A. & Seed, B. Proc. natn. Acad. Sci. U.S.A. 84, 8573–8477 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sánchez, I., Hughes, R., Mayer, B. et al. Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature 372, 794–798 (1994). https://doi.org/10.1038/372794a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/372794a0
This article is cited by
-
The ginsenoside Rg2 downregulates MMP-1 expression in keratinocyte (HaCaT)-conditioned medium-treated human fibroblasts (Hs68)
Applied Biological Chemistry (2023)
-
Extracellular Signal-Regulated Kinase1 (ERK1)-Mediated Phosphorylation of Voltage-Dependent Anion Channel (VDAC) Suppresses its Conductance
The Journal of Membrane Biology (2022)
-
The AP-1 family of transcription factors are important regulators of gene expression within Leydig cells
Endocrine (2021)
-
Long noncoding RNA LINC01111 suppresses pancreatic cancer aggressiveness by regulating DUSP1 expression via microRNA-3924
Cell Death & Disease (2019)
-
Stress-induced ceramide generation and apoptosis via the phosphorylation and activation of nSMase1 by JNK signaling
Cell Death & Differentiation (2015)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.