As we all know, erythropoietin is secreted predominantly by the kidney (85% from the kidney, 15% from the liver) in response to hypoxia and its function is to stimulate erythropoiesis in the bone marrow. What is the receptor on which erythropoietin works?
The Epo receptor is a member of the cytokine receptor family expressed on the cell surface of erythroid precursors. Although the Epo receptor itself does not have kinase activity, it is bound by the tyrosine kinase Jak2, also called Janus kinase 2. The activation of downstream transcription factors by Jak2 (e.g., the Stat family of transcription factors) results in accelerated erythrocyte maturation.
Interestingly, a common mutation in the Jak2 gene (V617F) accounts for the majority of cases of polycythemia vera–the hematologic condition in which there is a primary elevation in the hematocrit which can result in thrombotic complications. These patients have a low circulating EPO level, but as the EPO receptor is constitutively active, there is always accelerated erythropoeisis.