Signal transduction through the receptor for erythropoietin

Erythropoietin (EPO) supports the proliferation and differentiation of erythroid lineage cells. The receptor for erythropoietin is a member of the cytokine receptor family. Introduction of EPOR into IL-3 dependent cells confers the ability to proliferate in response to EPO. Associated with this, EPO induces the expression of a number of immediate-early response genes. Mutagenesis studies have addressed the function role of various motifs and domains in receptor function and established essential roles for the conserved cysteines and the WSXWS motif. The signal transducing pathways activated by EPOR include induction of tyrosine phosphorylation. Within the cytoplasmic domain a relatively small membrane proximal region is essential for induction of tyrosine phosphorylation, expression of immediate early genes and for mitogenesis. The role of various kinases in this response is discussed as well as an assessment of potential substrates of tyrosine phosphorylation.