Gene Set: NUMATA_CSF3_SIGNALING_VIA_STAT3

Standard name NUMATA_CSF3_SIGNALING_VIA_STAT3
Systematic name M1454
Brief description Target genes for STAT3 [GeneID=20848] in CSF3 [GeneID=12985] signaling during myeloblast differentiation to neutrophils.
Full description or 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15664994   Authors: Numata A,Shimoda K,Kamezaki K,Haro T,Kakumitsu H,Shide K,Kato K,Miyamoto T,Yamashita Y,Oshima Y,Nakajima H,Iwama A,Aoki K,Takase K,Gondo H,Mano H,Harada M
Exact source Table 1
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Organism Mus musculus
Contributed by Kevin Vogelsang (MSigDB Team)
Source platform MOUSE_SEQ_ACCESSION
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Version history 3.1: First introduced

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