EPOR Human, Active

The erythropoietin receptor (EPOR) is a protein that plays a crucial role in the regulation of red blood cell production. It is a member of the cytokine receptor family and is primarily expressed on the surface of erythroid progenitor cells in the bone marrow. The receptor is activated by erythropoietin (EPO), a glycoprotein hormone produced mainly by the kidneys in response to hypoxia (low oxygen levels).

The erythropoietin receptor is a transmembrane protein composed of an extracellular domain, a single transmembrane helix, and an intracellular domain. The extracellular domain is responsible for binding to erythropoietin, while the intracellular domain is involved in signal transduction. Upon binding of erythropoietin to the receptor, a conformational change occurs, leading to the activation of intracellular signaling pathways that promote the survival, proliferation, and differentiation of erythroid progenitor cells into mature red blood cells .

Recombinant human erythropoietin receptor (rhEPOR) is produced using recombinant DNA technology. This involves the insertion of the human EPOR gene into a suitable expression system, such as mammalian cells, which then produce the receptor protein. The recombinant receptor retains the same structure and biological activity as the naturally occurring receptor, making it a valuable tool for research and therapeutic applications .

1. Research: Recombinant human erythropoietin receptor is widely used in research to study the mechanisms of erythropoiesis (red blood cell production) and to investigate the signaling pathways activated by erythropoietin. It is also used to screen for potential therapeutic agents that can modulate the activity of the receptor.

2. Therapeutics: The recombinant receptor is used in the development of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia, particularly in patients with chronic kidney disease, cancer, or those undergoing chemotherapy. These agents mimic the action of erythropoietin by binding to the erythropoietin receptor and stimulating red blood cell production .

The binding of erythropoietin to its receptor triggers a cascade of intracellular signaling events. The primary signaling pathway involves the activation of the Janus kinase 2 (JAK2) and the subsequent phosphorylation of the signal transducer and activator of transcription 5 (STAT5). This leads to the transcription of genes that are essential for erythroid progenitor cell survival, proliferation, and differentiation .

Mutations or dysregulation of the erythropoietin receptor can lead to various hematological disorders. For example, gain-of-function mutations in the EPOR gene can result in primary familial and congenital polycythemia, a condition characterized by an increased red blood cell mass. Conversely, loss-of-function mutations can lead to anemia .