The erythropoietin receptor: Structure, activation and intracellular signal transduction

Erythropoietin (Epo) and its receptor (EpoR) are essential for proliferatio n, differentiation and survival of erythroid progenitors. Here, we review s everal mechanisms by which the EpoR can be activated. We also describe the many intracellular signal transduction pathways activated by the EpoR. None ave unique to the EpoR and mutant receptors able to activate only a subset of these pathways can support erythropoiesis in EpoR(-/-) fetal liver cell s. Furthermore, normal erythroid differentiation occurs when the EpoR is re placed by the prolactin receptor or the myeloid oncoprotein Bcr-abl, Epo an d probably other growth factors are required merely to ensure the survival and proliferation of already committed progenitors.