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A possible involvement of Stat5 in erythropoietin-induced hemoglobin synthesis.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 1997 May 08; Vol. 234 (1), pp. 198-205. - Publication Year :
- 1997
-
Abstract
- Erythropoietin (EPO) and its cell surface receptor (EPOR) play central roles in the proliferation and differentiation of mammalian erythroid progenitor cells. Recently both the tyrosine residues in the EPOR responsible for the activation of Stat5 and the role of Stat5 for EPO-dependent cell proliferation have been shown. Here, we describe the roles of Stat5 and of these tyrosine residues in the EPOR in the erythroid differentiation of murine hematopoietic cell line SKT6 which produces hemoglobin in response to EPO. Chimeric receptors carrying the extracellular domain of the EGF receptor and the intracellular domain of the EPOR were introduced into SKT6 cells. Like EPO, EGF equally activated Stat5 and induced hemoglobin. Activation of Stat5 and hemoglobin expression by EGF were markedly impaired in cells expressing the tyrosine mutated chimeric receptors. In addition, ectopic expression of the prolactin receptor, another cytokine receptor that activates Stat5, led to hemoglobin synthesis. Finally, hemoglobin synthesis was severely inhibited by overexpressing a dominant negative form of Stat5. These results collectively suggest that Stat5 plays a role in EPO-mediated hemoglobin synthesis in SKT6 cells.
- Subjects :
- Animals
Cell Line
DNA-Binding Proteins genetics
Epidermal Growth Factor pharmacology
ErbB Receptors genetics
ErbB Receptors metabolism
Erythropoiesis
Gene Expression Regulation
Histocytochemistry
Immunoblotting
Janus Kinase 2
Mice
Phosphorylation
Prolactin pharmacology
Protein-Tyrosine Kinases metabolism
Receptors, Erythropoietin metabolism
Receptors, Prolactin metabolism
Recombinant Fusion Proteins metabolism
STAT5 Transcription Factor
Signal Transduction physiology
Spleen
Trans-Activators genetics
Tyrosine metabolism
DNA-Binding Proteins metabolism
Erythropoietin pharmacology
Hemoglobins biosynthesis
Milk Proteins
Proto-Oncogene Proteins
Trans-Activators metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 234
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 9168989
- Full Text :
- https://doi.org/10.1006/bbrc.1997.6486