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

FEBS Lett. 2001 Sep 7;505(1):168-72. doi: 10.1016/s0014-5793(01)02810-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anisomycin / pharmacology
  • Cell Differentiation*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Erythroid Precursor Cells / metabolism*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Hemin / pharmacology
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • K562 Cells
  • MAP Kinase Kinase 4*
  • MAP Kinase Kinase 7
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Protein Isoforms
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism
  • Staurosporine / pharmacology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Enzyme Inhibitors
  • Heat-Shock Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins c-jun
  • Transcription Factors
  • HSF2 protein, human
  • Anisomycin
  • Hemin
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • MAP Kinase Kinase 7
  • MAP2K4 protein, human
  • MAP2K7 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • Staurosporine