| Interleukin-7-induced Stat-5 acts in synergy with Flt-3 signaling to stimulate expansion of hematopoietic progenitor cells. | |
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MedLine Citation:
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PMID: 20829349 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The development of lymphoid cells from bone marrow progenitors is dictated by interplay between internal cues such as transcription factors and external signals like the cytokines Flt-3 ligand and Il-7. These proteins are both of large importance for normal lymphoid development; however, it is unclear if they act in direct synergy to expand a transient Il-7R(+)Flt-3(+) population or if the collaboration is created through sequential activities. We report here that Flt-3L and Il-7 synergistically stimulated the expansion of primary Il-7R(+)Flt-3(+) progenitor cells and a hematopoietic progenitor cell line ectopically expressing the receptors. The stimulation resulted in a reduced expression of pro-apoptotic genes and also mediated survival of primary progenitor cells in vitro. However, functional analysis of single cells suggested that the anti-apoptotic effect was additive indicating that the synergy observed mainly depends on stimulation of proliferation. Analysis of downstream signaling events suggested that although Il-7 induced Stat-5 phosphorylation, Flt-3L caused activation of the ERK and AKT signaling pathways. Flt-3L could also drive proliferation in synergy with ectopically expressed constitutively active Stat-5. This synergy could be inhibited with either receptor tyrosine kinase or MAPK inhibitors suggesting that Flt-3L and Il-7 act in synergy by activation of independent signaling pathways to expand early hematopoietic progenitors. |
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Authors:
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Josefine Åhsberg; Panagiotis Tsapogas; Hong Qian; Jenny Zetterblad; Sasan Zandi; Robert Månsson; Jan-Ingvar Jönsson; Mikael Sigvardsson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-09 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-15 Completed Date: 2011-02-28 Revised Date: 2012-06-05 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 36275-84 Citation Subset: IM |
Affiliation:
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Department of Clinical and Experimental Medicine, Experimental Hematopoiesis Unit, Faculty for Health Sciences, IKE Linköping University, 58185 Linköping, Sweden. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Blotting, Western Cell Proliferation* Cells, Cultured Drug Synergism Flow Cytometry Hematopoietic Stem Cells / cytology*, metabolism* Interleukin-7 / pharmacology* MAP Kinase Signaling System Mice Mice, Inbred C57BL Phosphatidylinositol 3-Kinases / metabolism Phosphorylation RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction STAT5 Transcription Factor / genetics, metabolism* Signal Transduction* fms-Like Tyrosine Kinase 3 / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-7; 0/RNA, Messenger; 0/STAT5 Transcription Factor; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Flt3 protein, mouse; EC 2.7.10.1/fms-Like Tyrosine Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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