Abstract
One Ras-dependent protein kinase cascade leading from growth factor receptors to the ERK (extracellular signal-regulated kinases) subgroup of mitogen-activated protein kinases (MAPKs) is dependent on the protein kinase Raf-1, which activates the MEK (MAPK or ERK kinase) dual specificity kinases. A second protein kinase cascade leading to activation of the Jun kinases (JNKs) is dependent on MEKK (MEK kinase). A dual-specificity kinase that activates JNK, named JNKK, was identified that functions between MEKK and JNK. JNKK activated the JNKs but did not activate the ERKs and was unresponsive to Raf-1 in transfected HeLa cells. JNKK also activated another MAPK, p38 (Mpk2; the mammalian homolog of HOG1 from yeast), whose activity is regulated similarly to that of the JNKs.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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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Cell Line
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Enzyme Activation
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Epidermal Growth Factor / pharmacology
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HeLa Cells
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Humans
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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MAP Kinase Kinase Kinase 1*
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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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Phosphorylation
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Protein Kinases / chemistry
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-raf
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Recombinant Fusion Proteins / metabolism
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Substrate Specificity
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Transfection
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p38 Mitogen-Activated Protein Kinases
Substances
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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Epidermal Growth Factor
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Protein Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-raf
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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 Kinase 1
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MAP3K1 protein, human
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases