Activation of Stat 5b in erythroid progenitors correlates with the ability of ErbB to induce sustained cell proliferation.
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.
Mellitzer
G
G
Institute of Molecular Pathology, Vienna, Austria.
Wessely
O
O
Decker
T
T
Meinke
A
A
Hayman
M J
MJ
Beug
H
H
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
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