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.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 9000468 Publication Model: Print Cited Medium: Print ISSN: 0897-7194 (Print) Linking ISSN: 08977194 NLM ISO Abbreviation: Growth Factors Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: Chur ; New York : Harwood Academic Publishers, 1988-

Milk Proteins* ; Proto-Oncogene Proteins*; DNA-Binding Proteins/*genetics ; Erythroid Precursor Cells/*metabolism ; Erythropoietin/*pharmacology ; Hemoglobins/*biosynthesis ; Receptors, Erythropoietin/*metabolism ; Receptors, Prolactin/*genetics ; Transcription Factors/*genetics; Amino Acid Sequence ; Animals ; DNA-Binding Proteins/metabolism ; ErbB Receptors/chemistry ; ErbB Receptors/genetics ; Erythroid Precursor Cells/cytology ; Erythroid-Specific DNA-Binding Factors ; GATA1 Transcription Factor ; Gene Expression Regulation, Developmental ; Hemoglobins/genetics ; Janus Kinase 2 ; Kruppel-Like Transcription Factors ; Leukemia, Erythroblastic, Acute ; Mice ; Mice, Inbred Strains ; Molecular Sequence Data ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/metabolism ; Receptors, Erythropoietin/chemistry ; Receptors, Erythropoietin/genetics ; Receptors, Prolactin/metabolism ; Recombinant Fusion Proteins/pharmacology ; STAT1 Transcription Factor ; STAT3 Transcription Factor ; STAT5 Transcription Factor ; Signal Transduction ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Tumor Cells, Cultured

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.

DK40242 United States DK NIDDK NIH HHS; HL03042 United States HL NHLBI NIH HHS

0 (DNA-Binding Proteins)
0 (Erythroid-Specific DNA-Binding Factors)
0 (GATA1 Transcription Factor)
0 (Gata1 protein, mouse)
0 (Hemoglobins)
0 (Kruppel-Like Transcription Factors)
0 (Milk Proteins)
0 (Proto-Oncogene Proteins)
0 (Receptors, Erythropoietin)
0 (Receptors, Prolactin)
0 (Recombinant Fusion Proteins)
0 (STAT1 Transcription Factor)
0 (STAT3 Transcription Factor)
0 (STAT5 Transcription Factor)
0 (Stat1 protein, mouse)
0 (Stat3 protein, mouse)
0 (Trans-Activators)
0 (Transcription Factors)
0 (erythroid Kruppel-like factor)
11096-26-7 (Erythropoietin)
EC 2.7.10.1 (ErbB Receptors)
EC 2.7.10.1 (Protein-Tyrosine Kinases)
EC 2.7.10.2 (Jak2 protein, mouse)
EC 2.7.10.2 (Janus Kinase 2)

Date Created: 19970101 Date Completed: 19970909 Latest Revision: 20191102

20250114

10.3109/08977199709021518

9255607