Control of erythroid differentiation: possible role of the transferrin cycle.
A monoclonal antibody to the chicken transferrin receptor (JS-8) blocked temperature-induced and spontaneous differentiation of avian erythroid cells transformed by ts- and wt-retroviral oncogenes. In cells committed to differentiate, JS-8 caused an arrest at the erythroblast or early reticulocyte stage, followed by premature cell death, whereas proliferation of noncommitted erythroid cells or other hematopoietic cells remained unaffected. JS-8 had no effect on transferrin binding or internalization, but blocked subsequent receptor-recycling resulting in reduced iron uptake. Restoration of high intracellular iron levels neutralized the action of JS-8, whereas an inhibitor of porphyrine biosynthesis (4,6-dioxoheptanoic acid) closely mimicked the effect of JS-8. This suggests that erythroid differentiation might involve coordinate synthesis of erythrocyte proteins subject to regulation by hemin or hemoglobin.
D001355:Alpharetrovirus; D000818:Animals; D000911:Antibodies, Monoclonal; D001059:Apoproteins; D001692:Biological Transport; D002453:Cell Cycle; D002454:Cell Differentiation; D002472:Cell Transformation, Viral; D002645:Chickens; D003207:Conalbumin / Q000378:metabolism; D004920:Erythropoiesis; D004921:Erythropoietin / Q000502:physiology; D006427:Hemin / Q000172:deficiency; D007158:Immunologic Techniques; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology; D011166:Porphyrins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000502:physiology*; D011990:Receptors, Transferrin; D014168:Transferrin / Q000378:metabolism / Q000502:physiology*
D000911:Antibodies, Monoclonal; D001059:Apoproteins; D007502:Iron Chelating Agents; D011166:Porphyrins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin; C028284:apotransferrin; D004921:Erythropoietin; D003207:Conalbumin; D006427:Hemin; D007501:Iron