Proliferation and erythroid differentiation through the cytoplasmic domain of the erythropoietin receptor.
Interaction of erythropoietin (EPO) and its membrane receptor induces the proliferation and differentiation of erythroid progenitors. The molecular mechanism of the EPO receptor-mediated signal transduction remains unclear because the cloned EPO receptor does not contain any enzyme-related or nucleotide-binding consensus sequences in its cytoplasmic domain. We have previously shown that epidermal growth factor (EGF) induces dimerization of a chimeric receptor carrying the extracellular domain of the EGF receptor linked to the cytoplasmic domain of the EPO receptor, resulting in producing proliferation signals in interleukin-3-dependent cells. Here we show that this chimeric receptor transmits an EGF-dependent erythroid differentiation signal in the EPO-responsive erythroleukemia cell line, TSA8. EGF as well as EPO had little effect on the proliferation of TSA8 cells expressing the chimeric receptor, but both of them induced globin synthesis in these cells. Moreover, a truncated chimeric receptor carrying the membrane proximal 127 amino acids of the cytoplasmic domain of the EPO receptor linked to the extracellular domain of the EGF receptor conferred EGF-dependent proliferation on Ba/F3 cells and globin induction on TSA8 cells. These findings indicate that the membrane proximal region of the cytoplasmic domain of the EPO receptor is sufficient to produce both proliferation and differentiation signals if it is properly activated by receptor dimerization.
Maruyama
K
K
Department of Pediatrics, Faculty of Medicine, Kagoshima University, Japan.
Miyata
K
K
Yoshimura
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D005914:Globins / Q000096:biosynthesis; D006410:Hematopoiesis / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D009838:Oligodeoxyribonucleotides; D017467:Receptors, Erythropoietin; D011993:Recombinant Fusion Proteins; D005914:Globins; D066246:ErbB Receptors