title: Activation of Stat 5b in erythroid progenitors correlates with the ability of ErbB to induce sustained cell proliferation.
abstract: Self renewal of normal erythroid progenitors is induced by the receptor tyrosine kinase c-ErbB, whereas other receptors (c-Kit/Epo-R) regulate erythroid differentiation. To address possible mechanisms that could explain this selective activity of c-ErbB, we analyzed the ability of these receptors to activate the different members of the Stat transcription factor family. Ligand activation of c-ErbB induced the tyrosine phosphorylation, DNA-binding, and reporter gene transcription of Stat 5b in erythroblasts. In contrast, ligand activation of c-Kit was unable to induce any of these effects in the same cells. Activation of the erythropoietin receptor caused specific DNA-binding of Stat 5b, but failed to induce reporter gene transcription. These biochemical findings correlate perfectly with the selective ability of c-ErbB to cause sustained self renewal in erythroid progenitors.
authors.affiliation: Institute of Molecular Pathology, Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Mellitzer
authors.forename: O
authors.initials: O
authors.lastname: Wessely
authors.forename: T
authors.initials: T
authors.lastname: Decker
authors.forename: A
authors.initials: A
authors.lastname: Meinke
authors.forename: M J
authors.initials: MJ
authors.lastname: Hayman
authors.forename: H
authors.initials: H
authors.lastname: Beug
mesh_terms: D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism*; D018815:Genes, erbB; D006801:Humans; D008894:Milk Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017467:Receptors, Erythropoietin / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014369:Tryptophan-tRNA Ligase / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D008894:Milk Proteins; D017467:Receptors, Erythropoietin; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D016211:Transforming Growth Factor alpha; D014443:Tyrosine; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D014369:Tryptophan-tRNA Ligase; C073175:WARS1 protein, human