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

Akihiko Numata, Kazuya Shimoda, Kenjiro Kamezaki, Takashi Haro, Haruko Kakumitsu, Koutarou Shide, Kouji Kato, Toshihiro Miyamoto, Yoshihiro Yamashita, Yasuo Oshima, Hideaki Nakajima, Atsushi Iwama, Kenichi Aoki, Ken Takase, Hisashi Gondo, Hiroyuki Mano, Mine Harada

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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/EBPα was up-regulated by the activation of Stat3. In addition, activated Stat3 bound to CCAAT/enhancer-binding protein (C/EBP)α, leading to the enhancement of the transcription activity of C/EBPα. Conditional expression of C/EBPα 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/EBPα 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/EBPα, which is essential for myeloid differentiation. Additionally, cooperation of C/EBPα with other Stat3-activated proteins are required for the induction of some G-CSF responsive genes including lysozyme M and the G-CSF receptor.

Original languageEnglish
Pages (from-to)12621-12629
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number13
DOIs
Publication statusPublished - Apr 1 2005

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CCAAT-Enhancer-Binding Proteins
STAT3 Transcription Factor
Granulocyte Colony-Stimulating Factor
Clone Cells
Granulocyte Colony-Stimulating Factor Receptors
Lipocalins
Gelatinases
Cells
Muramidase
Genes
Janus Kinases
Cell Line
Interleukin-3
Cell proliferation
Transcription
Transcriptome
Granulocytes
Gene expression
Restoration
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein α in granulocyte colony-stimulating factor signaling pathway. / Numata, Akihiko; Shimoda, Kazuya; Kamezaki, Kenjiro; Haro, Takashi; Kakumitsu, Haruko; Shide, Koutarou; Kato, Kouji; Miyamoto, Toshihiro; Yamashita, Yoshihiro; Oshima, Yasuo; Nakajima, Hideaki; Iwama, Atsushi; Aoki, Kenichi; Takase, Ken; Gondo, Hisashi; Mano, Hiroyuki; Harada, Mine.

In: Journal of Biological Chemistry, Vol. 280, No. 13, 01.04.2005, p. 12621-12629.

Research output: Contribution to journalArticle

Numata, Akihiko ; Shimoda, Kazuya ; Kamezaki, Kenjiro ; Haro, Takashi ; Kakumitsu, Haruko ; Shide, Koutarou ; Kato, Kouji ; Miyamoto, Toshihiro ; Yamashita, Yoshihiro ; Oshima, Yasuo ; Nakajima, Hideaki ; Iwama, Atsushi ; Aoki, Kenichi ; Takase, Ken ; Gondo, Hisashi ; Mano, Hiroyuki ; Harada, Mine. / Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein α in granulocyte colony-stimulating factor signaling pathway. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 13. pp. 12621-12629.
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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/EBPα was up-regulated by the activation of Stat3. In addition, activated Stat3 bound to CCAAT/enhancer-binding protein (C/EBP)α, leading to the enhancement of the transcription activity of C/EBPα. Conditional expression of C/EBPα 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/EBPα 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/EBPα, which is essential for myeloid differentiation. Additionally, cooperation of C/EBPα with other Stat3-activated proteins are required for the induction of some G-CSF responsive genes including lysozyme M and the G-CSF receptor.",
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AU - Numata, Akihiko

AU - Shimoda, Kazuya

AU - Kamezaki, Kenjiro

AU - Haro, Takashi

AU - Kakumitsu, Haruko

AU - Shide, Koutarou

AU - Kato, Kouji

AU - Miyamoto, Toshihiro

AU - Yamashita, Yoshihiro

AU - Oshima, Yasuo

AU - Nakajima, Hideaki

AU - Iwama, Atsushi

AU - Aoki, Kenichi

AU - Takase, Ken

AU - Gondo, Hisashi

AU - Mano, Hiroyuki

AU - Harada, Mine

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N2 - 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/EBPα was up-regulated by the activation of Stat3. In addition, activated Stat3 bound to CCAAT/enhancer-binding protein (C/EBP)α, leading to the enhancement of the transcription activity of C/EBPα. Conditional expression of C/EBPα 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/EBPα 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/EBPα, which is essential for myeloid differentiation. Additionally, cooperation of C/EBPα with other Stat3-activated proteins are required for the induction of some G-CSF responsive genes including lysozyme M and the G-CSF receptor.

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