Abstract
Mitogen-activated protein/ERK kinase kinases (MEKKs) phosphorylate and activate protein kinases which in turn phosphorylate and activate the p42/44 mitogen-activated protein kinase (MAPK), c-Jun/stress-activated protein kinases (JNKs), and p38/Hog1 kinase. We have isolated the cDNAs for two novel mammalian MEKKs (MEKK 2 and 3). MEKK 2 and 3 encode proteins of 69.7 and 71 kDa, respectively. The kinase domains encoded in the COOH-terminal moiety are 94% conserved; the NH2-terminal moieties are approximately 65% homologous, suggesting this region may encode sequences conferring differential regulation of the two kinases. Expression of MEKK 2 or 3 in HEK293 cells results in activation of p42/44MAPK and JNK but not of p38/Hog1 kinase. Immunoprecipitated MEKK 2 phosphorylated the MAP kinase kinases, MEK 1, and JNK kinase. Titration of MEKK 2 and 3 expression in transfection assays indicated that MEKK 2 preferentially activated JNK while MEKK 3 preferentially activated p42/44MAPK. These findings define a family of MEKK proteins capable of regulating sequential protein kinase pathways involving MAPK members.
Publication types
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Comparative Study
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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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Antibodies
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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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Cloning, Molecular
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Conserved Sequence
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DNA Primers
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DNA, Complementary
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Humans
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JNK Mitogen-Activated Protein Kinases
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Kinetics
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MAP Kinase Kinase 2
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MAP Kinase Kinase 3
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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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Peptide Fragments / chemical synthesis
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Peptide Fragments / immunology
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Phosphorylation
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Polymerase Chain Reaction
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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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Protein-Tyrosine Kinases / biosynthesis
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Protein-Tyrosine Kinases / chemistry
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Protein-Tyrosine Kinases / metabolism*
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Recombinant Proteins / biosynthesis
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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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Antibodies
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DNA Primers
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DNA, Complementary
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Peptide Fragments
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Recombinant Proteins
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MAP2K2 protein, human
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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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MAP Kinase Kinase 2
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MAP Kinase Kinase 3
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MAP2K3 protein, human
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Mitogen-Activated Protein Kinase Kinases
Associated data
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GENBANK/U43186
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GENBANK/U43187