= Erythropoietin receptor
The \b[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.<JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin by B. A. Witthuhn and others>[Abstract: EPOR lacks an intrinsic kinase domain; ligand-dependent JAK2 phosphorylation and activation.]{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.<JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin by B. A. Witthuhn and others>[Primary association, phosphorylation, in-vitro autophosphorylation and EPOR-mutant experiments.]{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.
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