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Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration

Erythropoietin (EPO), a humoral regulator of erythropoiesis and replacement therapy for selected red blood cell disorders in EPO-deficient patients, has been implicated in a wide range of activities on diverse cell, tissue, and organ types. EPO signals via two receptors, one comprising EPO receptor...

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Autor principal: Broxmeyer, Hal E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570099/
https://www.ncbi.nlm.nih.gov/pubmed/23401569
http://dx.doi.org/10.1084/jem.20122760
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author Broxmeyer, Hal E.
author_facet Broxmeyer, Hal E.
author_sort Broxmeyer, Hal E.
collection PubMed
description Erythropoietin (EPO), a humoral regulator of erythropoiesis and replacement therapy for selected red blood cell disorders in EPO-deficient patients, has been implicated in a wide range of activities on diverse cell, tissue, and organ types. EPO signals via two receptors, one comprising EPO receptor (EPOR) homodimers and the other a heterodimer of EPOR and CD131—the common β chain component of the GM-CSF, interleukin (IL)-3, and IL-5 receptors. Ligation of EPORs triggers various signaling pathways, including the JAK2–STAT5 and MAPK–NF-κB pathways, depending both on the receptor and the target cell type. A new study in this issue reveals a novel EPO-triggered pathway involving a Spi2A serpin–lysosome–cathepsin cascade that is initiated through the homodimeric EPOR complex and is required for the survival of erythroid progenitors. A full understanding of EPO’s effects on various cell types and their potential clinical relevance requires more work on the signaling events initiated through both EPORs, the effects of other cytokines and growth factors that modulate EPO’s actions, and a comparison of the effects of full-length versus truncated forms of EPO.
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spelling pubmed-35700992013-08-11 Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration Broxmeyer, Hal E. J Exp Med Minireview Erythropoietin (EPO), a humoral regulator of erythropoiesis and replacement therapy for selected red blood cell disorders in EPO-deficient patients, has been implicated in a wide range of activities on diverse cell, tissue, and organ types. EPO signals via two receptors, one comprising EPO receptor (EPOR) homodimers and the other a heterodimer of EPOR and CD131—the common β chain component of the GM-CSF, interleukin (IL)-3, and IL-5 receptors. Ligation of EPORs triggers various signaling pathways, including the JAK2–STAT5 and MAPK–NF-κB pathways, depending both on the receptor and the target cell type. A new study in this issue reveals a novel EPO-triggered pathway involving a Spi2A serpin–lysosome–cathepsin cascade that is initiated through the homodimeric EPOR complex and is required for the survival of erythroid progenitors. A full understanding of EPO’s effects on various cell types and their potential clinical relevance requires more work on the signaling events initiated through both EPORs, the effects of other cytokines and growth factors that modulate EPO’s actions, and a comparison of the effects of full-length versus truncated forms of EPO. The Rockefeller University Press 2013-02-11 /pmc/articles/PMC3570099/ /pubmed/23401569 http://dx.doi.org/10.1084/jem.20122760 Text en © 2013 Broxmeyer This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Minireview
Broxmeyer, Hal E.
Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration
title Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration
title_full Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration
title_fullStr Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration
title_full_unstemmed Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration
title_short Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration
title_sort erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration
topic Minireview
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570099/
https://www.ncbi.nlm.nih.gov/pubmed/23401569
http://dx.doi.org/10.1084/jem.20122760
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