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dc.contributor.authorEvans, Caroline A
dc.contributor.authorPierce, Andrew
dc.contributor.authorWinter, Sandra A
dc.contributor.authorSpooncer, Elaine
dc.contributor.authorHeyworth, Clare M
dc.contributor.authorWhetton, Anthony D
dc.date.accessioned2010-02-08T11:39:30Z
dc.date.available2010-02-08T11:39:30Z
dc.date.issued1999-09-01
dc.identifier.citationActivation of granulocyte-macrophage colony-stimulating factor and interleukin-3 receptor subunits in a multipotential hematopoietic progenitor cell line leads to differential effects on development. 1999, 94 (5):1504-14 Blooden
dc.identifier.issn0006-4971
dc.identifier.pmid10477674
dc.identifier.urihttp://hdl.handle.net/10541/91379
dc.description.abstractActivation of specific cytokine receptors promotes survival and proliferation of hematopoietic progenitor cells but their role in the control of differentiation is unclear. To address this issue, the effects of human interleukin-3 (hIL-3) and human granulocyte-macrophage colony-stimulating factor (hGM-CSF) on hematopoietic development were investigated in hematopoietic progenitor cells. Murine multipotent factor-dependent cell-Paterson (FDCP)-mix cells, which can self-renew or differentiate, were transfected with the genes encoding the unique alpha and/or shared beta(c) human hIL-3 receptor (hIL-3 R) or hGM-CSF receptor (hGM R) subunits by retroviral gene transfer. Selective activation of hIL-3 Ralpha,beta(c) or hGM Ralpha,beta(c) transfects by hIL-3 and hGM-CSF promoted self-renewal and myeloid differentiation, respectively, over a range of cytokine (0.1 to 100 ng/mL) concentrations. These qualitatively distinct developmental outcomes were associated with different patterns of protein tyrosine phosphorylation and, thus, differential signaling pathway activation. The cell lines generated provide a model to investigate molecular events underlying self-renewal and differentiation and indicate that the alpha subunits act in combination with the hbeta(c) to govern developmental decisions. The role of the alpha subunit in conferring specificity was studied by using a chimeric receptor composed of the extracellular hIL-3 Ralpha and intracellular hGM Ralpha subunit domains. This receptor promoted differentiation in response to hIL-3. Thus, the alpha subunit cytosolic domain is an essential component in determining cell fate via specific signaling events.
dc.language.isoenen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals
dc.subject.meshCell Differentiation
dc.subject.meshCell Line
dc.subject.meshCells, Cultured
dc.subject.meshGene Expression Regulation, Developmental
dc.subject.meshGene Transfer Techniques
dc.subject.meshGenetic Vectors
dc.subject.meshHematopoiesis
dc.subject.meshHematopoietic Stem Cells
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshReceptors, Granulocyte-Macrophage Colony-Stimulating Factor
dc.subject.meshReceptors, Interleukin-3
dc.subject.meshRetroviridae
dc.titleActivation of granulocyte-macrophage colony-stimulating factor and interleukin-3 receptor subunits in a multipotential hematopoietic progenitor cell line leads to differential effects on development.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biomolecular Sciences, Leukaemia Research Fund Cellular Development Unit, Manchester, United Kingdom.en
dc.identifier.journalBlooden
html.description.abstractActivation of specific cytokine receptors promotes survival and proliferation of hematopoietic progenitor cells but their role in the control of differentiation is unclear. To address this issue, the effects of human interleukin-3 (hIL-3) and human granulocyte-macrophage colony-stimulating factor (hGM-CSF) on hematopoietic development were investigated in hematopoietic progenitor cells. Murine multipotent factor-dependent cell-Paterson (FDCP)-mix cells, which can self-renew or differentiate, were transfected with the genes encoding the unique alpha and/or shared beta(c) human hIL-3 receptor (hIL-3 R) or hGM-CSF receptor (hGM R) subunits by retroviral gene transfer. Selective activation of hIL-3 Ralpha,beta(c) or hGM Ralpha,beta(c) transfects by hIL-3 and hGM-CSF promoted self-renewal and myeloid differentiation, respectively, over a range of cytokine (0.1 to 100 ng/mL) concentrations. These qualitatively distinct developmental outcomes were associated with different patterns of protein tyrosine phosphorylation and, thus, differential signaling pathway activation. The cell lines generated provide a model to investigate molecular events underlying self-renewal and differentiation and indicate that the alpha subunits act in combination with the hbeta(c) to govern developmental decisions. The role of the alpha subunit in conferring specificity was studied by using a chimeric receptor composed of the extracellular hIL-3 Ralpha and intracellular hGM Ralpha subunit domains. This receptor promoted differentiation in response to hIL-3. Thus, the alpha subunit cytosolic domain is an essential component in determining cell fate via specific signaling events.


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