Erythropoietin receptor

The erythropoietin receptor is a cell-surface cytokine receptor through which erythropoietin regulates the survival, proliferation and differentiation of developing red-cell precursors during erythropoiesis. It connects an extracellular hormone signal to intracellular responses; it is not the oxygen-carrying pigment of a mature red blood cell.

The erythropoietin receptor lacks its own catalytic kinase domain. Instead it associates with JAK2, a protein kinase that can be activated after erythropoietin stimulation. This provides an example of a receptor that recruits enzymatic signaling machinery rather than catalyzing the phosphorylation reaction itself.^[ref]

The 1993 experiments compared receptor-associated JAK2 before and after hormone stimulation and tested receptor mutants. Erythropoietin induced tyrosine phosphorylation of JAK2 and increased its measured kinase activity; the behavior of receptor mutants connected this signaling response to stimulated cell proliferation. Combining physical association, biochemical activity and functional responses was stronger evidence than observing receptor binding alone.^[ref]

The distinction also clarifies timescales. Binding a hormone can alter signaling rapidly, while changing the population of circulating red blood cells requires the downstream production and maturation process. Receptor activation and a later change in hematocrit are related measurements at different biological levels.