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 c-Jun N-terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. 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.
Hietakangas
V
V
Turku Centre for Biotechnology, University of Turku, Abo Akademi University, Finland.
Elo
I
I
Rosenström
H
H
Coffey
E T
ET
Kyriakis
J M
JM
Eriksson
J E
JE
Sistonen
L
L
D000841:Anisomycin / Q000494:pharmacology; D002454:Cell Differentiation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020014:K562 Cells; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020033:Protein Isoforms; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D020033:Protein Isoforms; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; C070389:HSF2 protein, human; D000841:Anisomycin; D006427:Hemin; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482559:MAP2K4 protein, human; C482569:MAP2K7 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D019311:Staurosporine