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http://purl.uniprot.org/citations/19109256http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19109256http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19109256http://www.w3.org/2000/01/rdf-schema#comment"Interleukin-3 (IL-3) promotes both self-renewal and differentiation of early multipotential progenitors and is involved in inducible hematopoiesis in response to infections. Here we report new insights into these processes with the identification of a new isoform (SP2) of IL-3 receptor alpha (IL-3Ralpha), present in mouse and human hematopoietic cells, which lacks domain 1 of the full-length receptor (SP1). Binding assays with beta(IL-3) mutants showed that mouse SP2 uses a different high affinity binding mode to SP1, although both mouse and human SP2 and SP1 can stimulate IL-3-dependent growth. In IL-3-dependent differentiation models, human SP2 and SP1 gave differential effects on lineage commitment or self-renewal dependent on the cellular context, suggesting that different modes of ectodomain binding may modulate intracellular signaling. In a multipotential factor dependent cell-Paterson mix, the transcription factors C/EBPalpha and PU.1 and microRNAs miRNA-15a, -223, and -181a were up-regulated in cells undergoing SP2-supported differentiation compared with SP1-supported self-renewal. Similarly in M1 cells, SP2 promoted differentiation compared with SP1 and gave up-regulation of PU.1 and miRNA-155 and -223. These findings suggest that IL-3-promoted lineage commitment uses similar mechanisms to those of steady-state hematopoiesis. Both the SP1 and SP2 isoforms activated the Jak2/STAT5, Akt, and Erk1/2 signaling pathways in M1 cells, although the activation was more prolonged for the SP2 isoform."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m808197200"xsd:string
http://purl.uniprot.org/citations/19109256http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m808197200"xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Chen J."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Chen J."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Olsen J."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Olsen J."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Young I.G."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Young I.G."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Walker A."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Walker A."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Murphy J.M."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Murphy J.M."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Ford S."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Ford S."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Mirza S."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/author"Mirza S."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/pages"5763-5773"xsd:string
http://purl.uniprot.org/citations/19109256http://purl.uniprot.org/core/pages"5763-5773"xsd:string