Erythropoietin-induced erythroid differentiation of the human erythroleukemia cell line TF-1 correlates with impaired STAT5 activation.
The TF-1 cell line has been established from a patient with erythroleukemia. While various cytokines induce TF-1 cell proliferation, erythropoietin (Epo) only sustains the short-term growth of these cells and induces their differentiation along the erythroid lineage. A truncated Epo receptor (EpoR) is overexpressed in these cells. The truncation removed the 96 C-terminal amino acids, including seven tyrosine residues. An additional single mutation at position +3 of Tyr344 led to the replacement of leucine 347 by proline. Stimulation by Epo induced an impaired activation of the STAT5 transcription factor in these cells. The same defect in STAT5 activation was found in the murine FDCP-1 cell line transfected with a chimeric EpoR containing the abnormal TF-1 EpoR cytoplasmic domain. Infection of TF-1 cells with a retrovirus containing a normal murine EpoR was able to restore both Epo-induced STAT5 activity and cellular proliferation. In contrast, Epo-induced differentiation was reduced strongly in infected TF-1ER cells. These results suggest that Epo-induced differentiation correlates with impaired Epo-induced STAT5 activation.
Chrétien
S
S
Institut National de la Transfusion Sanguine (INTS), Paris, France.
Varlet
P
P
Verdier
F
F
Gobert
S
S
Cartron
J P
JP
Gisselbrecht
S
S
Mayeux
P
P
Lacombe
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051379:Mice; D008894:Milk Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000187:drug effects*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D017467:Receptors, Erythropoietin / Q000187:drug effects* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor; D017384:Sequence Deletion; D015398:Signal Transduction / Q000187:drug effects*; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D009363:Neoplasm Proteins; D017467:Receptors, Erythropoietin; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D004921:Erythropoietin