title: Erythropoietin receptor response circuits.
abstract: OBJECTIVE
  In 1985-1989, erythropoietin (EPO), its receptor (EPOR), and janus kinase 2 were cloned; established to be essential for definitive erythropoiesis; and initially intensely studied. Recently, new impetus, tools, and model systems have emerged to re-examine EPO/EPOR actions, and are addressed in this review. Impetus includes indications that EPO affects significantly more than standard erythroblast survival pathways, the development of novel erythropoiesis-stimulating agents, increasing evidence for EPO/EPOR cytoprotection of ischemically injured tissues, and potential EPO-mediated worsening of tumorigenesis.
  
  
  RESULTS
  New findings are reviewed in four functional contexts: (pro)erythroblast survival mechanisms, new candidate EPO/EPOR effects on erythroid cell development and new EPOR responses, EPOR downmodulation and trafficking, and novel erythropoiesis-stimulating agents.
  
  
  CONCLUSIONS
  As Current Opinion, this monograph seeks to summarize, and provoke, new EPO/EPOR action concepts. Specific problems addressed include: beyond (and before) BCL-XL, what key survival factors are deployed in early-stage proerythroblasts? Are distinct EPO/EPOR signals transduced in stage-selective fashions? Is erythroblast proliferation also modulated by EPO/EPOR signals? What functions are subserved by new noncanonical EPO/EPOR response factors (e.g. podocalyxin like-1, tribbles 3, reactive oxygen species, and nuclear factor kappa B)? What key regulators mediate EPOR inhibition and trafficking? And for emerging erythropoiesis-stimulating agents, to what extent do activities parallel EPOs (or differ in advantageous, potentially complicating ways, or both)?
authors.affiliation: Center of Excellence in Stem Cell Biology and Regenerative Medicine, Maine Medical Center Research Institute, Scarborough, Maine, USA. wojchd@mmc.org
authors.forename: Don M
authors.initials: DM
authors.lastname: Wojchowski
authors.forename: Pradeep
authors.initials: P
authors.lastname: Sathyanarayana
authors.forename: Arvind
authors.initials: A
authors.lastname: Dev
mesh_terms: D000818:Animals; D004900:Erythroblasts / Q000502:physiology*; D004921:Erythropoietin / Q000378:metabolism*; D006801:Humans; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin