CCAAT/enhancer binding protein ε: Changes in function upon phosphorylation by p38 MAP kinase

Elizabeth A. Williamson, Ian K. Williamson, Alexey M. Chumakov, Alan D. Friedman, H. Phillip Koeffler

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

C/EBPε, a member of the CCAAT/enhancer binding protein family, is a transcription factor important in neutrophil differentiation. We have determined that it is phosphorylated on multiple serine and threonine residues and can be a target for phosphorylation by a number of kinases. We identified a threonine at amino acid 75, part of a consensus mitogen-activated protein (MAP) kinase site within the transactivation domain of C/EBPε, as being phosphorylated only by p38 MAP kinase. Phosphorylation of this residue resulted in enhanced transcriptional activity on a myeloid-specific promoter in in vitro transient transfection reporter assays. We also determined that phosphorylation at Thr75 yielded a protein that was more effective at binding its cognate DNA sequence compared with the wild-type nonphosphorylated C/EBPε. Stable expression of C/EBPεT75A in interleukin 3 (IL-3)-dependent 32Dc13 did not result in the up-regulation of expression of secondary granule genes compared with wild-type C/EBPε or C/EBPεT75D. Therefore we suggest that C/EBPε is a target for p38 MAP kinase activity.

Original languageEnglish (US)
Pages (from-to)3841-3847
Number of pages7
JournalBlood
Volume105
Issue number10
DOIs
StatePublished - May 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Williamson, E. A., Williamson, I. K., Chumakov, A. M., Friedman, A. D., & Koeffler, H. P. (2005). CCAAT/enhancer binding protein ε: Changes in function upon phosphorylation by p38 MAP kinase. Blood, 105(10), 3841-3847. https://doi.org/10.1182/blood-2004-09-3708