Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Erythropoietin Receptor

  • Thierry DarribèreEmail author
  • Xavier Bigard
  • Michèle BeaudryEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101844



Historical Background

The erythropoietin receptor (EPOR) and its cognate ligand, erythropoietin (EPO), are required for maintaining adequate levels of circulating erythrocytes during embryogenesis and adulthood by promoting erythroid mitogenesis, survival, and differentiation. Before the cloning of the EPOR cDNA, radiolabeled EPO was used to demonstrate specific binding to normal erythroid progenitors, murine and human erythroleukemia cells, and cells from human fetal liver. Then in 1989, the EPOR cDNA has been cloned by transfection of recombinant plasmid pools of murine cDNA from murine erythroleukemia (MEL) cell line into COS cells. A single cDNA was isolated that confers to COS cells the ability to bind EPO (D’Andrea et al. 1989). This murine EPOR cDNA, expressed in COS cells, generates high-affinity (30 pM) and low-affinity (210 pM) receptors. In 1990, the human homologue of the murine EPORhas been isolated from an erythroleukemia line and from fetal liver (Jones...

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  1. Arcasoy MO, Jiang X, Haroon ZA. Expression of erythropoietin receptor splice variants in human cancer. Biochem Biophys Res Commun. 2003;307(4):999–1007.CrossRefPubMedGoogle Scholar
  2. Bento C, McMullin MF, Percy M, Cario H. Primary familial and congenital polycythemia. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, LJH B, et al., editors. GeneReviews. Seattle: University of Washington; 2016.Google Scholar
  3. Brines M, Cerami A. Discovering erythropoietin’s extra-hematopoietic functions: biology and clinical promise. Kidney Int. 2006;70:246–50.PubMedCrossRefGoogle Scholar
  4. Budarf M, Huebner K, Emanuel B, Croce CM, Copeland NG, Jenkins NA, D’Andrea AD. Assignment of the erythropoietin receptor (EPOR) gene to mouse chromosome 9 and human chromosome 19. Genomics. 1990;8:575–8.CrossRefPubMedGoogle Scholar
  5. Chen G, Shi JX, Hang CH, Xie W, Liu J, Liu X. Inhibitory effect on cerebral inflammatory agents that accompany traumatic brain injury in a rat model: a potential neuroprotective mechanism of recombinant human erythropoietin (rhEPO). Neurosci Lett. 2007;425:177–1782.CrossRefPubMedGoogle Scholar
  6. Constantinescu SN, Huang LJ, Nam H, Lodish HF. The erythropoietin receptor cytosolic juxtamembrane domain contains an essential, precisely oriented, hydrophobic motif. Mol Cell. 2001;7:377–85.CrossRefPubMedGoogle Scholar
  7. D’Andrea AD, Lodish HF, Wong GG. Expression cloning of the murine erythropoietin receptor. Cell. 1989;57:277–85.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Debeljak N, Solár P, Sytkowski AJ. Erythropoietin and cancer: the unintended consequences of anemia correction. Front Immunol. 2014;5:563–76.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Hardee ME, Murat O, Arcasoy K, Blackwell L, Kirkpatrick JP, Dewhirst MW. Erythropoietin biology in cancer. Clin Cancer Res. 2006;12:332–9.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003;102:1340–6.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Huang LJ, Shen YM, Bulut GB. Advances in understanding the pathogenesis of primary familial and congenital polycythemia. Br J Haematol. 2010;148:844–52.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Iacobucci I, Li Y, Roberts KG, Dobson SM, Kim JC, Payne-Turner D, et al. Truncating erythropoietin receptor rearrangements in acute lymphoblastic leukemia. Cancer Cell. 2016;29(2):186–200.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Jones SS, D’Andrea AD, Haines LL, Wong GG. Human erythropoietin receptor: cloning, expression, and biologic characterization. Blood. 1990;76(1):31–5.PubMedGoogle Scholar
  14. Kubatzky KF, Moucadel V, Constentinescu S. Signal transduction of the erythropoietin receptor: role of the transmembrane region. Hématologie. 2005;11:19–28.Google Scholar
  15. McCaffery PJ, Fraser JK, Lin FK, Berridge MV. Subunit structure of the erythropoietin receptor. J Biol Chem. 1989;264(18):10507–12.PubMedGoogle Scholar
  16. Ogunshola OO, Bogdanova AY. Epo and non-hematopoietic cells: what do we know? Methods Mol Biol. 2013;982:13–41.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Paffett-Lugassy N, Hsia N, Fraenkel PG, Paw B, Leshinsky I, Barut B, et al. Functional conservation of erythropoietin signaling in zebrafish. Blood. 2007;110:2718–26.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Satoh K, Kagaya Y, Nakano M, Ito Y, Ohta J, Tada H, et al. Important role of endogenous erythropoietin system in recruitment of endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice. Circulation. 2006;113:1442–50.CrossRefPubMedGoogle Scholar
  19. Szenajch J, Wcislo G, Jeong JY, Szczylik C, Feldman L. The role of erythropoietin and its receptor in growth, survival and therapeutic response of human tumor cells from clinic to bench – a critical review. Biochim Biophys Acta. 2010;1806(1):82–95.PubMedCentralPubMedGoogle Scholar
  20. Teng R, Calvert JW, Sibmooh N, Piknova B, Suzuki N, Sun J, et al. Acute erythropoietin cardioprotection is mediated by endothelial response. Basic Res Cardiol. 2011;106:343–54.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Tsai PT, Ohab JJ, Kertesz N, Groszer M, Matter C, Gao J, et al. A critical role of erythropoietin receptor in neurogenesis and post-stroke recovery. J Neurosci. 2006;26:1269–74.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Xu X, Cao Z, Cao B, Li J, Guo L, Que L, et al. Carbamylated erythropoietin protects the myocardium from acute ischemia/reperfusion injury through a PI3K/Akt-dependent mechanism. Surgery. 2009;146:506–14.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Yergeau DA, Schmerer M, Kuliyev E, Evans T, Mead PE. Cloning and expression pattern of the Xenopus erythropoietin receptor. Gene Expr Patterns. 2006;6(4):420–5.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Laboratoire de Biologie du développementSorbonne Universités, UPMC Universités Paris 06, CNRS, Institut de Biologie Paris Seine (LBD – IBPS)ParisFrance
  2. 2.Agence Française de Lutte contre le DopageParisFrance
  3. 3.Laboratoire Hypoxie et PoumonsSorbonne Paris cité Universités Paris 13Bobigny CedexFrance