Signal Transducers and Activators of Transcription 3 Augments the Transcriptional Activity of CCAAT/Enhancer-binding Protein α in Granulocyte Colony-stimulating Factor Signaling Pathway

Autor: Takashi Haro, Haruko Kakumitsu, Yoshihiro Yamashita, Koutarou Shide, Akihiko Numata, Hisashi Gondo, Hideaki Nakajima, Yasuo Oshima, Kazuya Shimoda, Ken Takase, Hiroyuki Mano, Toshihiro Miyamoto, Kouji Kato, Atsushi Iwama, Mine Harada, Kenjiro Kamezaki, Kenichi Aoki
Rok vydání: 2005
Předmět:
Time Factors
Transcription
Genetic
Neutrophils
Biochemistry
Mice
Granulocyte Colony-Stimulating Factor
Gene expression
Myeloid Cells
Promoter Regions
Genetic
STAT3
Genes
Dominant
Oligonucleotide Array Sequence Analysis
Oncogene Proteins
Ccaat-enhancer-binding proteins
Reverse Transcriptase Polymerase Chain Reaction
JAK-STAT signaling pathway
Cell Differentiation
Flow Cytometry
Lipocalins
DNA-Binding Proteins
Cytokines
Signal transduction
Granulocyte colony-stimulating factor receptor
Signal Transduction
STAT3 Transcription Factor
Blotting
Western
Immunoblotting
Biology
Cell Line
Lipocalin-2
Proto-Oncogene Proteins
CCAAT-Enhancer-Binding Protein-alpha
Animals
Humans
Immunoprecipitation
RNA
Messenger
Molecular Biology
Cell Proliferation
Interferon-alpha
Cell Biology
Molecular biology
Gene Expression Regulation
Trans-Activators
STAT protein
biology.protein
Interleukin-3
Muramidase
Janus kinase
Acute-Phase Proteins
Granulocytes
Zdroj: Journal of Biological Chemistry. 280:12621-12629
ISSN: 0021-9258
Popis: 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.
Databáze: OpenAIRE
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