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  • Title: The C-terminal cytoplasmic region of the granulocyte colony-stimulating factor receptor mediates apoptosis in maturation-incompetent murine myeloid cells.
    Author: Dong F, Pouwels K, Hoefsloot LH, Rozemuller H, Löwenberg B, Touw IP.
    Journal: Exp Hematol; 1996 Feb; 24(2):214-20. PubMed ID: 8641344.
    Abstract:
    Granulocyte colony-stimulating factor (G-CSF) promotes the survival and proliferation of myeloid progenitors and induces maturation of these cells toward terminally differentiated neutrophils. Using transfectants of the murine IL-3-dependent myeloid cell line 32D that express the human G-CSF receptor (32D/WT cells), we show here that G-CSF can also exert adverse effects on myeloid cell survival. Although initially enhancing IL-3-driven proliferation of 32D/WT cells, G-CSF strongly inhibited cell survival at later stages of culture. The loss of viability of 32D/WT cells following sustained G-CSF stimulation was not accompanied by progressive neutrophilic maturation. Instead, 32D/WT cells exhibited features characteristic of apoptosis. The apoptosis-inducing effect of G-CSF was seen at concentrations of IL-3 that could support long-term proliferation and survival of 32D/WT cells in the absence of G-CSF. Experiments with 32D cells expressing mutant forms of the G-CSF receptor revealed that the death signals were mediated exclusively through the membrane-distal cytoplasmic part of the G-CSF receptor, a region also involved in maturation signaling.
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