Nonhematopoietic effects of erythropoiesis-stimulating agents

  • Wolfgang Jelkmann
  • Reinhard Depping
  • Eric Metzen
Part of the Milestones in Drug Therapy book series (MDT)


Erythropoietin (EPO) was originally considered a hormone with action restricted to erythrocytic progenitors. The colony-forming units-erythroid (CFU-E) possess abundant EPO receptor (EPOR) molecules, and EPO is essential for their survival, proliferation, and differentiation. The mature functional human erythropoietic EPOR is a homodimer of two 484 amino acids transmembrane glycoproteins of approximately 60kDa. On binding of 1 EPO molecule, the EPOR dimer undergoes a conformational change that is transmitted to the cytosolic domain resulting in the autophosphorylation of EPOR-associated Janus protein tyrosine kinases 2 (JAK-2). The tyrosine phosphorylated EPOR dimer exhibits intracellular docking sites for signaling proteins containing SRC homology 2 (SH2) domains [1]. The specific roles of the various then-activated enzymes, such as phosphatidylinositol-3 kinase (PI-3K)/Akt, mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and transcription factors, such as signal transducer and activator of transcription 5 (STAT-5), with respect to survival, proliferation, and differentiation are only partly understood. Clearly, however, the action of EPO requires the presence of functional EPOR and of appropriate EPOR signaling molecules. Activation of the EPOR is terminated by JAK-2 dephosphorylation and internalization of the EPO/EPOR complex [2].


Endothelial Progenitor Cell Darbepoetin Alfa Recombinant Human Erythropoietin Erythropoietin Receptor EPOR Protein 
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Copyright information

© Birkhäuser Verlag/Switzerland 2009

Authors and Affiliations

  • Wolfgang Jelkmann
    • 1
  • Reinhard Depping
    • 1
  • Eric Metzen
    • 2
  1. 1.Institute of PhysiologyUniversity of LübeckLübeckGermany
  2. 2.Institute of PhysiologyUniversity Duisburg-EssenEssenGermany

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