Abstract
As essential mediators of red cell production, erythropoietin (EPO) and its cell surface receptor (EPO receptor [EPOR]) have been intensely studied. Early investigations defined basic mechanisms for hypoxia-inducible factor induction of EPO expression, and within erythroid progenitors EPOR engagement of canonical Janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5), rat sarcoma/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAS/MEK/ERK), and phosphatidylinositol 3-kinase (PI3K) pathways. Contemporary genetic, bioinformatic, and proteomic approaches continue to uncover new clinically relevant modulators of EPO and EPOR expression, and EPO's biological effects. This Spotlight review highlights such factors and their emerging roles during erythropoiesis and anemia.
© 2015 by The American Society of Hematology.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Anemia / genetics
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Anemia / metabolism
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Animals
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Erythroid Precursor Cells / cytology
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Erythroid Precursor Cells / metabolism*
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Erythropoiesis / physiology*
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Erythropoietin / biosynthesis*
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Erythropoietin / genetics
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression Regulation / physiology*
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Humans
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Janus Kinase 2 / genetics
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Janus Kinase 2 / metabolism
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MAP Kinase Signaling System / physiology*
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Rats
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Receptors, Erythropoietin / biosynthesis*
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Receptors, Erythropoietin / genetics
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STAT5 Transcription Factor / genetics
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STAT5 Transcription Factor / metabolism
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ras Proteins / genetics
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ras Proteins / metabolism
Substances
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EPO protein, human
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Receptors, Erythropoietin
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STAT5 Transcription Factor
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Erythropoietin
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Phosphatidylinositol 3-Kinases
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JAK2 protein, human
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Janus Kinase 2
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Extracellular Signal-Regulated MAP Kinases
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ras Proteins