Activation of granulocyte-macrophage colony-stimulating factor and interleukin-3 receptor subunits in a multipotential hematopoietic progenitor cell line leads to differential effects on development.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91379
Title:
Activation of granulocyte-macrophage colony-stimulating factor and interleukin-3 receptor subunits in a multipotential hematopoietic progenitor cell line leads to differential effects on development.
Authors:
Evans, Caroline A; Pierce, Andrew; Winter, Sandra A; Spooncer, Elaine; Heyworth, Clare M; Whetton, Anthony D
Abstract:
Activation 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.
Affiliation:
Department of Biomolecular Sciences, Leukaemia Research Fund Cellular Development Unit, Manchester, United Kingdom.
Citation:
Activation 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 Blood
Journal:
Blood
Issue Date:
1-Sep-1999
URI:
http://hdl.handle.net/10541/91379
PubMed ID:
10477674
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorEvans, Caroline Aen
dc.contributor.authorPierce, Andrewen
dc.contributor.authorWinter, Sandra Aen
dc.contributor.authorSpooncer, Elaineen
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorWhetton, Anthony Den
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.en
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
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