Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun (original) (raw)

Nature volume 372, pages 794–798 (1994)Cite this article

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.

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Authors and Affiliations

  1. Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital East, and Department of Medicine Harvard Medical School, 149 13th Street, Charlestown, Massachusetts, 02129, USA
    Irma Sánchez, Joseph Avruch & John M. Kyriakls
  2. Division of Hematology/Oncology, Harvard Medical School, 300 Longwood Avenue, Enders 650, Boston, Massachusetts, 02115, USA
    Rowland T. Hughes, Karen Yee & Leonard I. Zon
  3. Department of Microbiology and Molecular Genetics, Harvard Medical School, 300 Longwood Avenue, Enders 650, Boston, Massachusetts, 02115, USA
    Bruce J. Mayer
  4. Howard Hughes Medical Institute, Children's Hospital and ¶ Dana-Farber Cancer Institute, Harvard Medical School, 300 Longwood Avenue, Enders 650, Boston, Massachusetts, 02115, USA
    Bruce J. Mayer & Leonard I. Zon
  5. Ontario Cancer Institute, Princess Margaret Hospital, 500 Sherbourne Street, Toronto, Ontario, M4X 1K9, Canada
    James R. Woodgett

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  1. Irma Sánchez
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  2. Rowland T. Hughes
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  3. Bruce J. Mayer
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  4. Karen Yee
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  5. James R. Woodgett
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  6. Joseph Avruch
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  7. John M. Kyriakls
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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

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