Abstract
JNK/SAPKs are identified as new members of the MAPK family; they phosphorylate c-Jun protein in response to several cellular stimuli including ultraviolet irradiation, TNF and osmotic shock. We have identified a protein kinase, MUK, as an activator of the JNK-pathway, whose kinase domain shows significant homology to MAPKKK-related proteins such as c-Raf and MEKK. The over-expression of MUK or MEK kinase (MEKK) in NIH3T3 or COS1 cells results in the activation of JNK1 and the accumulation of a hyper-phosphorylated form of c-Jun. While MEKK also activates the ERK pathway, MUK is a rather selective activator of the JNK pathway. On the other hand, c-Raf activates the JNK pathway only slightly despite its remarkable ability to activate the ERK pathway. Even though we originally identified MUK as a MAPKKK-related protein kinase, a greater similarity to mixed lineage kinase (MLK) is found not only in the catalytic domain but also in the 'leucine-zipper'-like motifs located at the C-terminal side of the catalytic domain. The structural divergence between MUK and MEKK reveals the multiplicity of signaling pathways that activate JNK/SAPKs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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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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Chlorocebus aethiops
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Cloning, Molecular
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DNA Primers
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DNA, Complementary
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JNK Mitogen-Activated Protein Kinases
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Leucine Zippers
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MAP Kinase Kinase Kinase 1*
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MAP Kinase Kinase Kinases
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Mice
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Protein Kinases / biosynthesis
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Protein Kinases / chemistry
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases / biosynthesis
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins c-jun / metabolism
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RNA, Messenger / analysis
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RNA, Messenger / biosynthesis
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Rats
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Transfection
Substances
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DNA Primers
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DNA, Complementary
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Proto-Oncogene Proteins c-jun
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RNA, Messenger
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Recombinant Proteins
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Protein 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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MAP Kinase Kinase Kinase 1
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MAP Kinase Kinase Kinases
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Map3k1 protein, mouse
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mitogen-activated protein kinase kinase kinase 12
Associated data
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GENBANK/D49785
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GENBANK/U49953