Abstract
A cDNA encoding a novel member of the mitogen-activated protein kinase kinase (MAPKK) family, MAPKK6, was isolated and found to encode a protein of 334 amino acids, with a calculated molecular mass of 37 kDa that is 79% identical to MKK3. MAPKK6 was shown to phosphorylate and specifically activate the p38/MPK2 subgroup of the mitogen-activated protein kinase superfamily and could be demonstrated to be phosphorylated and activated in vitro by TAK1, a recently identified MAPKK kinase. MKK3 was also shown to be a good substrate for TAK1 in vitro. Furthermore, when co-expressed with TAK1 in cells in culture, both MAPKK6 and MKK3 were strongly activated. In addition, co-expression of TAK1 and p38/MPK2 in cells resulted in activation of p38/MPK2. These results indicate the existence of a novel kinase cascade consisting of TAK1, MAPKK6/MKK3, and p38/MPK2.
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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Autoantibodies / blood
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Base Sequence
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Behcet Syndrome / enzymology
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Behcet Syndrome / immunology
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / immunology
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Line
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DNA Probes / genetics
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DNA, Complementary / genetics
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Enzyme Activation
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HeLa Cells
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Humans
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In Vitro Techniques
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MAP Kinase Kinase 3
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MAP Kinase Kinase 6
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Mitogen-Activated Protein Kinase Kinases*
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Molecular Sequence Data
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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 / genetics
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Protein-Tyrosine Kinases / metabolism*
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Substrate Specificity
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Transfection
Substances
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Autoantibodies
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DNA Probes
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DNA, Complementary
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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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MAP Kinase Kinase 3
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MAP Kinase Kinase 6
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MAP2K3 protein, human
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MAP2K6 protein, human
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Mitogen-Activated Protein Kinase Kinases