Phosphorylation of C/EBPα Inhibits Granulopoiesis

Sarah E. Ross, Hanna S. Radomska, Bo Wu, Pu Zhang, Jonathon N. Winnay, L. Bajnok, Wendy S. Wright, Fred Schaufele, Daniel G. Tenen, Ormond A. MacDougald

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

CCAAT/enhancer-binding protein α (C/EBP(α) is one of the key transcription factors that mediate lineage specification and differentiation of multipotent myeloid progenitors into mature granulocytes. Although C/EBPα is known to induce granulopoiesis while suppressing monocyte differentiation, it is unclear how C/EBPα regulates this cell fate choice at the mechanistic level. Here we report that inducers of monocyte differentiation inhibit the alternate cell fate choice, that of granulopoiesis, through inhibition of C/EBPα. This inhibition is mediated by extracellular signal-regulated kinases 1 and/or 2 (ERK1/2), which interact with C/EBPα through an FXFP docking site and phosphorylate serine 21. As a consequence of C/EBPα phosphorylation, induction of granulocyte differentiation by C/EBPα or retinoic acid is inhibited. Our analysis of C/EBPα by fluorescent resonance energy transfer revealed that phosphorylation induces conformational changes in C/EBPα, increasing the distance between the amino termini of C/EBPα dimers. Thus, myeloid development is partly regulated by an ERK1/2-mediated change in the conformation of C/EBPα that favors monocyte differentiation by blocking granulopoiesis.

Original languageEnglish
Pages (from-to)675-686
Number of pages12
JournalMolecular and Cellular Biology
Volume24
Issue number2
DOIs
Publication statusPublished - Jan 2004

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Monocytes
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Phosphorylation
Granulocytes
CCAAT-Enhancer-Binding Proteins
Energy Transfer
Protein C
Tretinoin
Serine
Transcription Factors

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Ross, S. E., Radomska, H. S., Wu, B., Zhang, P., Winnay, J. N., Bajnok, L., ... MacDougald, O. A. (2004). Phosphorylation of C/EBPα Inhibits Granulopoiesis. Molecular and Cellular Biology, 24(2), 675-686. https://doi.org/10.1128/MCB.24.2.675-686.2004

Phosphorylation of C/EBPα Inhibits Granulopoiesis. / Ross, Sarah E.; Radomska, Hanna S.; Wu, Bo; Zhang, Pu; Winnay, Jonathon N.; Bajnok, L.; Wright, Wendy S.; Schaufele, Fred; Tenen, Daniel G.; MacDougald, Ormond A.

In: Molecular and Cellular Biology, Vol. 24, No. 2, 01.2004, p. 675-686.

Research output: Contribution to journalArticle

Ross, SE, Radomska, HS, Wu, B, Zhang, P, Winnay, JN, Bajnok, L, Wright, WS, Schaufele, F, Tenen, DG & MacDougald, OA 2004, 'Phosphorylation of C/EBPα Inhibits Granulopoiesis', Molecular and Cellular Biology, vol. 24, no. 2, pp. 675-686. https://doi.org/10.1128/MCB.24.2.675-686.2004
Ross, Sarah E. ; Radomska, Hanna S. ; Wu, Bo ; Zhang, Pu ; Winnay, Jonathon N. ; Bajnok, L. ; Wright, Wendy S. ; Schaufele, Fred ; Tenen, Daniel G. ; MacDougald, Ormond A. / Phosphorylation of C/EBPα Inhibits Granulopoiesis. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 2. pp. 675-686.
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