Abstract
We have identified a direct physical interaction between the stress signaling p38alpha MAP kinase and the mitogen-activated protein kinases ERK1 and ERK2 by affinity chromatography and coimmunoprecipitation studies. Phosphorylation and activation of p38alpha enhanced its interaction with ERK1/2, and this correlated with inhibition of ERK1/2 phosphotransferase activity. The loss of epidermal growth factor-induced activation and phosphorylation of ERK1/2 but not of their direct activator MEK1 in HeLa cells transfected with the p38alpha activator MKK6(E) indicated that activated p38alpha may sequester ERK1/2 and sterically block their phosphorylation by MEK1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anisomycin / pharmacology
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Brain / metabolism
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Chromatography, Affinity
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Cloning, Molecular
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DNA, Complementary / metabolism
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Enzyme Activation
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Glutathione Transferase / metabolism
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HeLa Cells
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Humans
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Imidazoles / pharmacology
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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Mitogen-Activated Protein Kinases / metabolism*
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Phosphorylation
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Precipitin Tests
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Protein Binding
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Pyridines / pharmacology
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Rats
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Recombinant Fusion Proteins / metabolism
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Stress, Physiological*
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p38 Mitogen-Activated Protein Kinases
Substances
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DNA, Complementary
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Imidazoles
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Pyridines
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Recombinant Fusion Proteins
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Anisomycin
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Glutathione Transferase
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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SB 203580