title: Distinct signaling from stem cell factor and erythropoietin in HCD57 cells.
abstract: 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.
authors.affiliation: Department of Pharmacology/Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Jacobs-Helber
authors.forename: K
authors.initials: K
authors.lastname: Penta
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.forename: A
authors.initials: A
authors.lastname: Lawson
authors.forename: S T
authors.initials: ST
authors.lastname: Sawyer
mesh_terms: 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
chemical_list: D019089:Stem Cell Factor; D004921:Erythropoietin; D014443:Tyrosine