The EPO receptor and signal transduction

The availability of biologically active i Sj.iabelled EPO facilitated the detection and study of cell surface receptors. In addition to erythroid precursors, various other cell lines were shown to express EPO receptors, at least when cultured in vitro. Many harboured two classes of receptors a high-affinity and a low-affinity form. Most appeared to express between 1000 and 3000 receptors/cell. Radiotracer experiments illustrated that the EPO receptor is rapidly internalized after ligand binding and the EPO-receptor complex is subsequently degraded within lysosomes. 

The EPO receptor is a member of the haemopoietic cytokine receptor superfamily. Its intracellular domain displays no known catalytic activity but it appears to couple directly to the JAK 2 kinase (Chapter 4), which probably promotes the early events of EPO signal transduction. Other studies have implicated additional possible signalling mechanisms, including the involvement of G proteins, protein kinase C and Ca2 +. The exact molecular events underlining EPO signal transduction remain to be elucidated in detail. 

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