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Signal Transducers and Activators of Transcription 3 Augments the Transcriptional Activity of CCAAT/Enhancer-binding Protein α in Granulocyte Colony-stimulating Factor Signaling Pathway
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-dependen...
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Published in: | The Journal of biological chemistry 2005-04, Vol.280 (13), p.12621-12629 |
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creator | 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 |
description | 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. |
doi_str_mv | 10.1074/jbc.M408442200 |
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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.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M408442200</identifier><identifier>PMID: 15664994</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acute-Phase Proteins - metabolism ; Animals ; Blotting, Western ; CCAAT-Enhancer-Binding Protein-alpha - metabolism ; Cell Differentiation ; Cell Line ; Cell Proliferation ; Cytokines - metabolism ; DNA-Binding Proteins - metabolism ; DNA-Binding Proteins - physiology ; Flow Cytometry ; Gene Expression Regulation ; Genes, Dominant ; Granulocyte Colony-Stimulating Factor - metabolism ; Granulocytes - cytology ; Granulocytes - metabolism ; Humans ; Immunoblotting ; Immunoprecipitation ; Interferon-alpha - metabolism ; Interleukin-3 - metabolism ; Lipocalin-2 ; Lipocalins ; Mice ; Muramidase - chemistry ; Muramidase - metabolism ; Myeloid Cells - metabolism ; Neutrophils - metabolism ; Oligonucleotide Array Sequence Analysis ; Oncogene Proteins - metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Signal Transduction ; STAT3 Transcription Factor ; Time Factors ; Trans-Activators - metabolism ; Trans-Activators - physiology ; Transcription, Genetic</subject><ispartof>The Journal of biological chemistry, 2005-04, Vol.280 (13), p.12621-12629</ispartof><rights>2005 © 2005 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-6b4417c2ccb40d98edc53f3d485ece61168d267cf4b6a45d36ac0686408078313</citedby><cites>FETCH-LOGICAL-c413t-6b4417c2ccb40d98edc53f3d485ece61168d267cf4b6a45d36ac0686408078313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0021925819605922$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3549,27924,27925,45780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15664994$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Numata, Akihiko</creatorcontrib><creatorcontrib>Shimoda, Kazuya</creatorcontrib><creatorcontrib>Kamezaki, Kenjiro</creatorcontrib><creatorcontrib>Haro, Takashi</creatorcontrib><creatorcontrib>Kakumitsu, Haruko</creatorcontrib><creatorcontrib>Shide, Koutarou</creatorcontrib><creatorcontrib>Kato, Kouji</creatorcontrib><creatorcontrib>Miyamoto, Toshihiro</creatorcontrib><creatorcontrib>Yamashita, Yoshihiro</creatorcontrib><creatorcontrib>Oshima, Yasuo</creatorcontrib><creatorcontrib>Nakajima, Hideaki</creatorcontrib><creatorcontrib>Iwama, Atsushi</creatorcontrib><creatorcontrib>Aoki, Kenichi</creatorcontrib><creatorcontrib>Takase, Ken</creatorcontrib><creatorcontrib>Gondo, Hisashi</creatorcontrib><creatorcontrib>Mano, Hiroyuki</creatorcontrib><creatorcontrib>Harada, Mine</creatorcontrib><title>Signal Transducers and Activators of Transcription 3 Augments the Transcriptional Activity of CCAAT/Enhancer-binding Protein α in Granulocyte Colony-stimulating Factor Signaling Pathway</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>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.</description><subject>Acute-Phase Proteins - metabolism</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>CCAAT-Enhancer-Binding Protein-alpha - metabolism</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>Cell Proliferation</subject><subject>Cytokines - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>DNA-Binding Proteins - physiology</subject><subject>Flow Cytometry</subject><subject>Gene Expression Regulation</subject><subject>Genes, Dominant</subject><subject>Granulocyte Colony-Stimulating Factor - metabolism</subject><subject>Granulocytes - cytology</subject><subject>Granulocytes - metabolism</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Immunoprecipitation</subject><subject>Interferon-alpha - metabolism</subject><subject>Interleukin-3 - metabolism</subject><subject>Lipocalin-2</subject><subject>Lipocalins</subject><subject>Mice</subject><subject>Muramidase - chemistry</subject><subject>Muramidase - metabolism</subject><subject>Myeloid Cells - metabolism</subject><subject>Neutrophils - metabolism</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oncogene Proteins - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Proto-Oncogene Proteins</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction</subject><subject>STAT3 Transcription Factor</subject><subject>Time Factors</subject><subject>Trans-Activators - metabolism</subject><subject>Trans-Activators - physiology</subject><subject>Transcription, Genetic</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFkc1q3DAUhUVpaCZpt10WrbrzRLJkWV4ak59CQgudQndGluQZBVuaSnKCH6vbPkSeqZp4IHRRooWEuN85XM4B4CNGa4xKenHfyfUdRZzSPEfoDVhhxElGCvzzLVghlOOsygt-Cs5CuEfp0Aq_A6e4YIxWFV2BP9_N1ooBbrywQU1S-wCFVbCW0TyI6NLX9ctUerOPxllIYD1tR21jgHGn_x0mq2epifNB2DR1vbm4tDthk3XWGauM3cJv3kVtLHz6DdN9nQymwck5ati4wdk5C9GM0yDiAb4SMu0Bl0Wf1SLuHsX8Hpz0Ygj6w_E9Bz-uLjfNTXb79fpLU99mkmISM9ZRikuZS9lRpCqulSxITxTlhZaaYcy4ylkpe9oxQQtFmJCIcZZCRSUnmJyDz4vv3rtfkw6xHU2QehiE1W4KLSsLlpdl8SqIyyLVRA7gegGldyF43bd7b0bh5xaj9lBrm2ptX2pNgk9H56kbtXrBjz0mgC-ATkE8GO3bII1OmSvjtYytcuZ_3n8BMhi1GA</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Numata, Akihiko</creator><creator>Shimoda, Kazuya</creator><creator>Kamezaki, Kenjiro</creator><creator>Haro, Takashi</creator><creator>Kakumitsu, Haruko</creator><creator>Shide, Koutarou</creator><creator>Kato, Kouji</creator><creator>Miyamoto, Toshihiro</creator><creator>Yamashita, Yoshihiro</creator><creator>Oshima, Yasuo</creator><creator>Nakajima, Hideaki</creator><creator>Iwama, Atsushi</creator><creator>Aoki, Kenichi</creator><creator>Takase, Ken</creator><creator>Gondo, Hisashi</creator><creator>Mano, Hiroyuki</creator><creator>Harada, Mine</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20050401</creationdate><title>Signal Transducers and Activators of Transcription 3 Augments the Transcriptional Activity of CCAAT/Enhancer-binding Protein α in Granulocyte Colony-stimulating Factor Signaling Pathway</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-6b4417c2ccb40d98edc53f3d485ece61168d267cf4b6a45d36ac0686408078313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acute-Phase Proteins - metabolism</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>CCAAT-Enhancer-Binding Protein-alpha - metabolism</topic><topic>Cell Differentiation</topic><topic>Cell Line</topic><topic>Cell Proliferation</topic><topic>Cytokines - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>DNA-Binding Proteins - physiology</topic><topic>Flow Cytometry</topic><topic>Gene Expression Regulation</topic><topic>Genes, Dominant</topic><topic>Granulocyte Colony-Stimulating Factor - metabolism</topic><topic>Granulocytes - cytology</topic><topic>Granulocytes - metabolism</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Immunoprecipitation</topic><topic>Interferon-alpha - metabolism</topic><topic>Interleukin-3 - metabolism</topic><topic>Lipocalin-2</topic><topic>Lipocalins</topic><topic>Mice</topic><topic>Muramidase - chemistry</topic><topic>Muramidase - metabolism</topic><topic>Myeloid Cells - metabolism</topic><topic>Neutrophils - metabolism</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oncogene Proteins - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Proto-Oncogene Proteins</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction</topic><topic>STAT3 Transcription Factor</topic><topic>Time Factors</topic><topic>Trans-Activators - metabolism</topic><topic>Trans-Activators - physiology</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Numata, Akihiko</creatorcontrib><creatorcontrib>Shimoda, Kazuya</creatorcontrib><creatorcontrib>Kamezaki, Kenjiro</creatorcontrib><creatorcontrib>Haro, Takashi</creatorcontrib><creatorcontrib>Kakumitsu, Haruko</creatorcontrib><creatorcontrib>Shide, Koutarou</creatorcontrib><creatorcontrib>Kato, Kouji</creatorcontrib><creatorcontrib>Miyamoto, Toshihiro</creatorcontrib><creatorcontrib>Yamashita, Yoshihiro</creatorcontrib><creatorcontrib>Oshima, Yasuo</creatorcontrib><creatorcontrib>Nakajima, Hideaki</creatorcontrib><creatorcontrib>Iwama, Atsushi</creatorcontrib><creatorcontrib>Aoki, Kenichi</creatorcontrib><creatorcontrib>Takase, Ken</creatorcontrib><creatorcontrib>Gondo, Hisashi</creatorcontrib><creatorcontrib>Mano, Hiroyuki</creatorcontrib><creatorcontrib>Harada, Mine</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Numata, Akihiko</au><au>Shimoda, Kazuya</au><au>Kamezaki, Kenjiro</au><au>Haro, Takashi</au><au>Kakumitsu, Haruko</au><au>Shide, Koutarou</au><au>Kato, Kouji</au><au>Miyamoto, Toshihiro</au><au>Yamashita, Yoshihiro</au><au>Oshima, Yasuo</au><au>Nakajima, Hideaki</au><au>Iwama, Atsushi</au><au>Aoki, Kenichi</au><au>Takase, Ken</au><au>Gondo, Hisashi</au><au>Mano, Hiroyuki</au><au>Harada, Mine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Signal Transducers and Activators of Transcription 3 Augments the Transcriptional Activity of CCAAT/Enhancer-binding Protein α in Granulocyte Colony-stimulating Factor Signaling Pathway</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>280</volume><issue>13</issue><spage>12621</spage><epage>12629</epage><pages>12621-12629</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15664994</pmid><doi>10.1074/jbc.M408442200</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Acute-Phase Proteins - metabolism Animals Blotting, Western CCAAT-Enhancer-Binding Protein-alpha - metabolism Cell Differentiation Cell Line Cell Proliferation Cytokines - metabolism DNA-Binding Proteins - metabolism DNA-Binding Proteins - physiology Flow Cytometry Gene Expression Regulation Genes, Dominant Granulocyte Colony-Stimulating Factor - metabolism Granulocytes - cytology Granulocytes - metabolism Humans Immunoblotting Immunoprecipitation Interferon-alpha - metabolism Interleukin-3 - metabolism Lipocalin-2 Lipocalins Mice Muramidase - chemistry Muramidase - metabolism Myeloid Cells - metabolism Neutrophils - metabolism Oligonucleotide Array Sequence Analysis Oncogene Proteins - metabolism Promoter Regions, Genetic Proto-Oncogene Proteins Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Signal Transduction STAT3 Transcription Factor Time Factors Trans-Activators - metabolism Trans-Activators - physiology Transcription, Genetic |
title | Signal Transducers and Activators of Transcription 3 Augments the Transcriptional Activity of CCAAT/Enhancer-binding Protein α in Granulocyte Colony-stimulating Factor Signaling Pathway |
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