A possible involvement of Stat5 in erythropoietin-induced hemoglobin synthesis.
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.
Wakao
H
H
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan. hwakao@hri.co.jp
Chida
D
D
Damen
J E
JE
Krystal
G
G
Miyajima
A
A
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D004920:Erythropoiesis; D004921:Erythropoietin / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006454:Hemoglobins / Q000096:biosynthesis*; D006651:Histocytochemistry; D015151:Immunoblotting; D053614:Janus Kinase 2; D051379:Mice; D008894:Milk Proteins; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011981:Receptors, Prolactin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D006454:Hemoglobins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D011981:Receptors, Prolactin; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D004921:Erythropoietin; D014443:Tyrosine; D004815:Epidermal Growth Factor; D011388:Prolactin; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2