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

摘要: Activation of specific cytokine receptors promotes survival and proliferation hematopoietic progenitor cells but their role in the control differentiation is unclear. To address this issue, effects human interleukin-3 (hIL-3) granulocyte-macrophage colony-stimulating factor (hGM-CSF) on development were investigated cells. Murine multipotent factor-dependent cell-Paterson (FDCP)-mix cells, which can self-renew or differentiate, transfected with genes encoding unique alpha and/or shared beta(c) hIL-3 receptor (hIL-3 R) hGM-CSF (hGM subunits by retroviral gene transfer. Selective activation Ralpha,beta(c) hGM transfects promoted self-renewal myeloid differentiation, respectively, over a range (0.1 to 100 ng/mL) concentrations. These qualitatively distinct developmental outcomes associated different patterns protein tyrosine phosphorylation and, thus, differential signaling pathway activation. The cell lines generated provide model investigate molecular events underlying indicate that act combination hbeta(c) govern decisions. subunit conferring specificity was studied using chimeric composed extracellular Ralpha intracellular domains. This response hIL-3. Thus, cytosolic domain an essential component determining fate via events.