Epo-induced hemoglobinization of SKT6 cells is mediated by minimal cytoplasmic domains of the Epo or prolactin receptors without modulation of GATA-1 or EKLF.
Interaction of erythropoietin with its type 1 receptor is essential to the development of late erythroid progenitor cells. Through the ectopic expression of receptor mutants in lymphoid and myeloid cell lines, insight has been gained regarding effectors that regulate Epo-induced proliferation. In contrast, effectors that regulate Epo-induced differentiation events (e.g. globin gene expression) are largely undefined. For in vitro studies of this pathway, erythroleukemic SKT6 cell sublines have been isolated which stably and efficiently hemoglobinize in response to Epo. Epo rapidly activated Jak2, STAT5 and detectably STATs 1 and 3, while no effects on GATA-1, EKLF or STAT5 expression were observed. Finally, efficient hemoglobinization of SKT6 cells was shown to be mediated by chimeric receptors comprised of the EGF receptor extracellular domain and truncated cytoplasmic subdomains of either the Epo receptor or the prolactin Nb2 receptor. This work further establishes SKT6 cells as an important model for studies of Epo-stimulated differentiation, and shows that this signaling pathway is promoted by a limited set of membrane-proximal receptor domains and effectors.
Reese
T T
TT
Graduate Program in Pathobiology, Pennsylvania State University, University Park 16802, USA.
Gregory
R C
RC
Sharlow
E R
ER
Pacifici
R E
RE
Crouse
J A
JA
Todokoro
K
K
Wojchowski
D M
DM
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D004921:Erythropoietin / Q000494:pharmacology*; D050982:GATA1 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D006454:Hemoglobins / Q000096:biosynthesis* / Q000235:genetics; D053614:Janus Kinase 2; D051741:Kruppel-Like Transcription Factors; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008815:Mice, Inbred Strains; D008894:Milk Proteins; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011981:Receptors, Prolactin / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D006454:Hemoglobins; D051741:Kruppel-Like Transcription Factors; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D011981:Receptors, Prolactin; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; D004921:Erythropoietin; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2