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.
MeSH terms
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Base Sequence
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Cell Division
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Cell Line
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Chloramphenicol O-Acetyltransferase / metabolism
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DNA / metabolism
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DNA-Binding Proteins / metabolism*
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Erythroid Precursor Cells / cytology
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Erythroid Precursor Cells / metabolism*
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Genes, erbB*
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Humans
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Milk Proteins*
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Molecular Sequence Data
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Phosphorylation
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Promoter Regions, Genetic
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Proto-Oncogene Proteins c-kit / metabolism*
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptors, Erythropoietin / metabolism
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STAT5 Transcription Factor
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Signal Transduction
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Trans-Activators / metabolism*
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Transcription, Genetic
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Transforming Growth Factor alpha / pharmacology
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Tryptophan-tRNA Ligase / metabolism
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Tyrosine / metabolism
Substances
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DNA-Binding Proteins
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Milk Proteins
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Receptors, Erythropoietin
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STAT5 Transcription Factor
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Trans-Activators
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Transforming Growth Factor alpha
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Tyrosine
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DNA
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Chloramphenicol O-Acetyltransferase
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Proto-Oncogene Proteins c-kit
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Receptor Protein-Tyrosine Kinases
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Tryptophan-tRNA Ligase
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WARS1 protein, human