Distinct signaling from stem cell factor and erythropoietin in HCD57 cells.
A recent report (Wu, H., Klingmuller, U., Besmer, P., and Lodish, H. F. (1995) Nature 377, 242-246) documents the interaction of the erythropoietin (EPO) receptor (EPOR) with the stem cell factor (SCF) receptor (c-KIT) and suggests that SCF acts through the EPOR. To elucidate the ability of SCF to affect the erythropoietin signaling pathway, we studied the effect of SCF on EPOR phosphorylation, SHC/ERK-1 activity, and cell proliferation and apoptosis in EPO-dependent HCD57 cells. Treatment of these cells with SCF resulted in phosphorylation of the EPOR. However, SCF-dependent phosphorylation of the EPOR did not initiate an EPO-like intracellular signal. SCF induced proliferation, SHC phosphorylation, and activation of ERK-1 but did not activate the JAK/STAT pathway. SCF stimulated SHC phosphorylation and ERK-1 activation independent of the EPOR in cells where the EPOR was down-regulated; the presence of the EPOR appeared to facilitate SCF activation of SHC and ERK-1. Furthermore, treatment of HCD57 cells with SCF increased cell number over a 3-day treatment, but apoptosis was observed in these cells. These data may illustrate two distinct pathways for erythroid cell proliferation and prevention of apoptosis in response to EPO, thereby providing a system to discriminate these intracellular signals.
Jacobs-Helber
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Department of Pharmacology/Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Penta
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Sun
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Lawson
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Sawyer
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D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004921:Erythropoietin / Q000378:metabolism* / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D019089:Stem Cell Factor / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D019089:Stem Cell Factor; D004921:Erythropoietin; D014443:Tyrosine