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 p38 alpha MAP kinase and the mitogen-activated protein kinases ERK1 and ERK2 by affinity chromatography and coimmunoprecipitation studies. Phosphorylation and activation of p38 alpha 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 p38 alpha activator MKK6(E) indicated that activated p38 alpha may sequester ERK1/2 and sterically block their phosphorylation by MEK1.