Display Settings:

Format

Send to:

Choose Destination
J Biol Chem. 2005 Apr 1;280(13):12621-9. Epub 2005 Jan 21.

Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein alpha in granulocyte colony-stimulating factor signaling pathway.

Author information

  • 1Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan.

Abstract

The Janus kinase (Jak)-Stat pathway plays an essential role in cytokine signaling. Granulocyte colony-stimulating factor (G-CSF) promotes granulopoiesis and granulocytic differentiation, and Stat3 is the principle Stat protein activated by G-CSF. Upon treatment with G-CSF, the interleukin-3-dependent cell line 32D clone 3(32Dcl3) differentiates into neutrophils, and 32Dcl3 cells expressing dominant-negative Stat3 (32Dcl3/DNStat3) proliferate in G-CSF without differentiation. Gene expression profile and quantitative PCR analysis of G-CSF-stimulated cell lines revealed that the expression of C/EBPalpha was up-regulated by the activation of Stat3. In addition, activated Stat3 bound to CCAAT/enhancer-binding protein (C/EBP)alpha, leading to the enhancement of the transcription activity of C/EBPalpha. Conditional expression of C/EBPalpha in 32Dcl3/DNStat3 cells after G-CSF stimulation abolishes the G-CSF-dependent cell proliferation and induces granulocytic differentiation. Although granulocyte-specific genes, such as the G-CSF receptor, lysozyme M, and neutrophil gelatinase-associated lipocalin precursor (NGAL) are regulated by Stat3, only NGAL was induced by the restoration of C/EBPalpha after stimulation with G-CSF in 32Dcl3/DNStat3 cells. These results show that one of the major roles of Stat3 in the G-CSF signaling pathway is to augment the function of C/EBPalpha, which is essential for myeloid differentiation. Additionally, cooperation of C/EBPalpha with other Stat3-activated proteins are required for the induction of some G-CSF responsive genes including lysozyme M and the G-CSF receptor.

PMID:
15664994
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk