STANDARD_NAME NUMATA_CSF3_SIGNALING_VIA_STAT3 SYSTEMATIC_NAME MM633 COLLECTION M2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/mouse/geneset/NUMATA_CSF3_SIGNALING_VIA_STAT3 NAMESPACE MOUSE_SEQ_ACCESSION DESCRIPTION_BRIEF Target genes for STAT3 [GeneID=20848] in CSF3 [GeneID=12985] signaling during myeloblast differentiation to neutrophils. DESCRIPTION_FULL 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 GEOID 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 CONTRIBUTOR Kevin Vogelsang CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 1 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AB005654,AB012290,AF068182,D26077,D50434,D83966,L31532,M21829,M60778,M62362,M74425,NM_007633,NM_009821,U31993,U53228,U91513,V00726,X16670,X57349,X59421,X74736,Y11091,Y14754 GENE_SYMBOLS Map2k7,Srpk1,Blnk,Kif3b,Madcam1,Ptpn13,,Mecom,Itgal,Cebpa,Htr3a,Ccne1,Runx1,Il17ra,Rora,Ninj1,Hbb-y,,Tfrc,Fli1,Mst1r,Mknk1,Map6 FOUNDER_NAMES