We have identified a direct physical interaction between the stress signali
ng p38 alpha MAP kinase and the mitogen-activated protein kinases ERK1 and
ERK2 by affinity chromatography and coimmunoprecipitation studies. Phosphor
ylation and activation of p38 alpha enhanced its interaction with ERK1/2, a
nd this correlated with inhibition of ERK1/2 phosphotransferase activity. T
he loss of epidermal growth factor-induced activation and phosphorylation o
f ERK1/2 but not of their direct activator MEK1 in HeLa cells transfected w
ith the p38 alpha activator MKK6(E) indicated that activated p38 alpha may
sequester ERK1/2 and sterically block their phosphorylation by MEK1.