Abstract
MAPK/ERK kinase kinase 2 (MEKK2) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family of protein kinases. MAP3Ks are components of a three-tiered protein kinase pathway in which a MAP3K phosphorylates and activates a mitogen-activated protein kinase kinase (MAP2K), which in turn activates a mitogen-activated protein kinase (MAPK). We have previously identified residues within protein kinase subdomain X in the MAP3K, MEKK1, that are critical for its interaction with the MAP2K, MKK4, and MEKK1-induced MKK4 activation. We report here that kinase subdomain X also plays a critical role in MEKK2 activity. Select point mutations in subdomain X impair MEKK2 phosphorylation of the MAP2Ks, MKK7 and MEK5, abolish MEKK2-induced activation of the MAPKs, JNK1 and ERK5, and diminish MEKK2-dependent activation of an AP-1 reporter gene. Interestingly, the spectrum of mutations in subdomain X of MEKK2 that affects its activity is overlapping with but not identical to those that have effects on MEKK1. Thus, mutations in subdomain X differentially affect MEKK2 and MEKK1.
Publication types
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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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Binding Sites
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COS Cells
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Chlorocebus aethiops
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DNA Primers
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Enzyme Activation
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HeLa Cells
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Humans
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MAP Kinase Kinase Kinase 1*
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MAP Kinase Kinase Kinase 2
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MAP Kinase Kinase Kinase 3
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MAP Kinase Kinase Kinase 4
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MAP Kinase Kinase Kinases / chemistry
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MAP Kinase Kinase Kinases / genetics
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MAP Kinase Kinase Kinases / metabolism*
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Mice
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Protein Kinases / chemistry
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Protein Kinases / genetics*
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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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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Restriction Mapping
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Sequence Alignment
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Sequence Homology, Amino Acid
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Transcription Factors / metabolism
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Transfection
Substances
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DNA Primers
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Recombinant Proteins
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Transcription Factors
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Protein Kinases
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Protein Serine-Threonine Kinases
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MAP Kinase Kinase Kinase 1
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MAP Kinase Kinase Kinase 2
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MAP Kinase Kinase Kinase 3
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MAP Kinase Kinase Kinase 4
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MAP Kinase Kinase Kinases
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MAP3K1 protein, human
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MAP3K2 protein, human
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MAP3K3 protein, human
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MAP3K4 protein, human
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Map3k1 protein, mouse
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Map3k2 protein, mouse
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Map3k3 protein, mouse
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Map3k4 protein, mouse