Erythropoietin receptor (EPOR) (EPOR)

The erythropoietin receptor (EPOR) is a member of the type I cytokine receptor family that is essential for the production of red blood cells (erythropoiesis) (UniProt P19235). It is primarily expressed on the surface of erythroid progenitor cells in the bone marrow, where it exists as a pre-formed homodimer or assembles into one upon ligand binding (PubMed: 10449511). When erythropoietin (EPO) binds to the EPOR homodimer, it induces a conformational change that activates the associated Janus kinase 2 (JAK2), triggering downstream signaling through STAT5, PI3K/Akt, and MAPK pathways (StatPearls: Erythropoietin). These signals prevent apoptosis and promote the proliferation and differentiation of erythroid cells into mature erythrocytes. Clinically, EPOR is the target of erythropoiesis-stimulating agents (ESAs) like epoetin alfa and darbepoetin alfa, which are used to treat anemia in patients with chronic kidney disease or those undergoing chemotherapy (FDA: Epogen Label). However, therapeutic activation of EPOR carries risks, including hypertension and increased thromboembolic events, particularly when hemoglobin levels are targeted above 11 g/dL (NIH: MedlinePlus). Overexpression or mutations in the EPOR pathway are also implicated in conditions like polycythemia vera, where red blood cell production becomes uncontrolled.

Other names

EPO-RErythropoietin receptor homodimerHematopoietin receptor

Agonism of the erythropoietin receptor to induce homodimerization and activate the JAK2/STAT5 signaling pathway, stimulating erythroid progenitor survival and differentiation.