STAT Signaling by Erythropoietin

Erythropoietin (Epo) is a 34 kDa glycoprotein hormone that controls red cell formation through promotion of survival, proliferation and differentiation of erythroid progenitors. Apart from red cell precursors, the erythropoietin receptor (EpoR) is expressed in neurons, endothelial cells and megakaryocytes. Binding of Epo to the EpoR triggers the activation of different signaling pathways by activation of Janus kinase 2 (JAK2), STAT5, STAT1 and STAT3, phosphatidylinositol (PI)-3-Kinase, modulators of Ras and MAP kinase signaling, and multiple tyrosine kinases, as reviewed in (1, 2). Regulation of STAT signaling, especially of STAT5, is a prominent cellular signaling event induced by Epo. Deregulation of STAT cellular localization and transcriptional activity has been described in a number of hematological malignancies, underscoring the importance of the STAT pathway for hematopoietic homeostasis