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

The stress-activated protein kinases (SAPKs), which are distantly related to the MAP kinases, are the dominant c-Jun amino-terminal protein kinases activated in response to a variety of cellular stresses, including treatment with tumour-necrosis factor-alpha and interleukin-beta (refs 1, 2). SAPK ph...

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Bibliographic Details
Published in:Nature (London) 1994-12, Vol.372 (6508), p.794-798
Main Authors: Sánchez, Irma, Hughes, Rowland T, Mayer, Bruce J, Yee, Karen, Woodgett, James R, Avruch, Joseph, Kyriakls, John M, Zon, Leonard I
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Biological and medical sciences
Brain - metabolism
Cancer
Cell Line
Cell physiology
Cellular biology
Cloning, Molecular
DNA, Complementary
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Genetics
Heat-Shock Proteins - metabolism
MAP Kinase Kinase 4
MAP Kinase Kinase Kinase 1
Mice
Mitogen-Activated Protein Kinase Kinases
Molecular and cellular biology
Molecular Sequence Data
Muscles - metabolism
Protein Kinases - genetics
Protein Kinases - metabolism
Protein-Serine-Threonine Kinases - metabolism
Proteins
Proto-Oncogene Proteins c-jun - genetics
Sequence Homology, Amino Acid
Signal Transduction
Substrate Specificity
Transcription, Genetic
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Summary:The stress-activated protein kinases (SAPKs), which are distantly related to the MAP kinases, are the dominant c-Jun amino-terminal protein kinases activated in response to a variety of cellular stresses, including treatment with tumour-necrosis factor-alpha and interleukin-beta (refs 1, 2). SAPK phosphorylation of c-Jun probably activates the c-Jun transactivation function. SAPKs are part of a signal transduction cascade related to, but distinct from, the MAPK pathway. We have now identified a novel protein kinase, called SAPK/ERK kinase-1 (SEK1), which is structurally related to the MAP kinase kinases (MEKs). 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.
ISSN:0028-0836
1476-4687
DOI:10.1038/372794a0