Abstract
A cDNA was cloned and expressed that encodes human stress-activated protein kinase kinase-4 (SKK4), a novel MAP kinase kinase family member whose mRNA is widely expressed in human tissues. SKK4 activated SAPK1/JNK in vitro, but not SAPK2a/p38, SAPK2b/p38beta, SAPK3/ERK6 or SAPK4. It appears to be the mammalian homologue of HEP, an activator of SAPK1/JNK in Drosophila. In human epithelial KB cells SKK4 and SKK1/MKK4 (another activator of SAPK1/JNK) were both activated by stressful stimuli, but only SKK4 was activated by proinflammatory cytokines. The identification of SKK4 explains why the major SAPK1/JNK activator detected in many mammalian cell extracts is chromatographically separable from SKK1/MKK4.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cloning, Molecular
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Cytokines / pharmacology
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Enzyme Activation
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Escherichia coli
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Humans
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Interleukin-1 / pharmacology
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JNK Mitogen-Activated Protein Kinases
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KB Cells
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MAP Kinase Kinase 4*
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MAP Kinase Kinase 7
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Mitogen-Activated Protein Kinase 12
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Mitogen-Activated Protein Kinase Kinases*
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Protein-Tyrosine Kinases / metabolism
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Recombinant Fusion Proteins / metabolism
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Sequence Analysis, DNA
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Sequence Homology, Amino Acid
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Substrate Specificity
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Tumor Necrosis Factor-alpha / pharmacology
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p38 Mitogen-Activated Protein Kinases
Substances
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Cytokines
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Interleukin-1
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Recombinant Fusion Proteins
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Tumor Necrosis Factor-alpha
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Protein Kinases
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Mitogen-Activated Protein Kinase 12
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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MAP Kinase Kinase 7
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MAP2K4 protein, human
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MAP2K7 protein, human
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Mitogen-Activated Protein Kinase Kinases