Activation of the MKK4-JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2-beta isoform

In this study we report the activation of e-Jun terminal kinase (JNK) in hu man K562 erythroleukemia cells undergoing hemin-mediated erythroid differen tiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The ac tivation of JNK occurs through activation of mitogen-activated protein kina se kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-direct ed phosphatases. We have previously shown that overexpression of the HSF2-b eta isoform inhibits the activation of HSF2 upon hemin-induced erythroid di fferentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2. (C) 2001 Fe deration of European Biochemical Societies. Published by Elsevier Science B .V. All rights reserved.