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

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

Research output: Contribution to journalArticle

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

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CCAAT-Enhancer-Binding Proteins
Phosphorylation
p38 Mitogen-Activated Protein Kinases
Threonine
Interleukin-3
DNA sequences
Mitogen-Activated Protein Kinases
Serine
Transcriptional Activation
Transfection
Assays
Neutrophils
Transcription Factors
Phosphotransferases
Up-Regulation
Genes
Amino Acids
Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

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

CCAAT/enhancer binding protein ε : Changes in function upon phosphorylation by p38 MAP kinase. / Williamson, Elizabeth A.; Williamson, Ian K.; Chumakov, Alexey M.; Friedman, Alan David; Koeffler, H. Phillip.

In: Blood, Vol. 105, No. 10, 15.05.2005, p. 3841-3847.

Research output: Contribution to journalArticle

Williamson, EA, Williamson, IK, Chumakov, AM, Friedman, AD & Koeffler, HP 2005, 'CCAAT/enhancer binding protein ε: Changes in function upon phosphorylation by p38 MAP kinase', Blood, vol. 105, no. 10, pp. 3841-3847. https://doi.org/10.1182/blood-2004-09-3708
Williamson, Elizabeth A. ; Williamson, Ian K. ; Chumakov, Alexey M. ; Friedman, Alan David ; Koeffler, H. Phillip. / CCAAT/enhancer binding protein ε : Changes in function upon phosphorylation by p38 MAP kinase. In: Blood. 2005 ; Vol. 105, No. 10. pp. 3841-3847.
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