Erythropoietin receptor response circuits.
Curr Opin Hematol
; 17(3): 169-76, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20173635
ABSTRACT
PURPOSE OF REVIEW 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. RECENT FINDINGS:
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.SUMMARY:
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)?
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Eritroblastos
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Eritropoetina
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Receptores da Eritropoetina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article