Stress-induced inhibition of ERK1 and ERK2 by direct interaction with p38 MAP kinase.
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.
Department of Medicine, Koerner Pavilion, University of British Columbia, Vancouver, British Columbia, Canada.
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H
Zhang
X
X
Shi
M
M
Hampong
L
L
Blanis
S
S
Pelech
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004789:Enzyme Activation; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013312:Stress, Physiological; D048051:p38 Mitogen-Activated Protein Kinases
D018076:DNA, Complementary; D007093:Imidazoles; D011725:Pyridines; D011993:Recombinant Fusion Proteins; D000841:Anisomycin; D005982:Glutathione Transferase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580