ArticleBlood2009
Ligand-induced EpoR internalization is mediated by JAK2 and p85 and is impaired by mutations responsible for primary familial and congenital polycythemia.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- Evaluating Transcriptomic Biomarkers for rHuEPO Detection: Assessing the Impact of Exercise and Altitude Exposure.Drug testing and analysis · 2026Article
- Stage-specific TRIM10 expression regulates erythroid maturation.EMBO reports · 2025Article
- Iron chelation improves ineffective erythropoiesis and iron overload in myelodysplastic syndrome mice.eLife · 2023Article
- Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesterase.Scientific reports · 2022Article
- The Presence of Circulating Nucleated Red Blood Cells Is Associated With Disease Severity in Patients of Hemorrhagic Fever With Renal Syndrome.Frontiers in medicine · 2021Article
- Erythropoietin regulation of red blood cell production: from bench to bedside and back.F1000Research · 2020Review
- MEKK3-MEK5-ERK5 signaling promotes mitochondrial degradation.Cell death discovery · 2020Article
- Enhanced anti-mammary gland cancer activities of tamoxifen-loaded erythropoietin-coated drug delivery system.PloS one · 2019Article
- New pathogenic mechanisms induced by germline erythropoietin receptor mutations in primary erythrocytosis.Haematologica · 2018Article
- Iron modulation of erythropoiesis is associated with Scribble-mediated control of the erythropoietin receptor.The Journal of experimental medicine · 2018Article
- Mechanisms of erythrocyte development and regeneration: implications for regenerative medicine and beyond.Development (Cambridge, England) · 2018Review
- Activating JAK2 mutants reveal cytokine receptor coupling differences that impact outcomes in myeloproliferative neoplasm.Leukemia · 2017Article
- Erythropoietin enhances Kupffer cell number and activity in the challenged liver.Scientific reports · 2017Article
- Correlated receptor transport processes buffer single-cell heterogeneity.PLoS computational biology · 2017Article
- Direct targets of pSTAT5 signalling in erythropoiesis.PloS one · 2017Article
- Erythropoietin Receptor Signaling and Lipid Rafts.Vitamins and hormones · 2017Review
- Cytokine Receptor Endocytosis: New Kinase Activity-Dependent and -Independent Roles of PI3K.Frontiers in endocrinology · 2017Review
- Plant-Produced Asialo-Erythropoietin Restores Pancreatic Beta-Cell Function by Suppressing Mammalian Sterile-20-like Kinase (MST1) and Caspase-3 Activation.Frontiers in pharmacology · 2017Article
- Oxygen-dependent Regulation of Erythropoietin Receptor Turnover and Signaling.The Journal of biological chemistry · 2016Article
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Epo-induced endocytosis of EpoR plays important roles in the down-regulation of EpoR signaling and is the primary means that regulates circulating Epo concentrations. Here we show that cell-surface EpoR is internalized via clathrin-mediated endocytosis. Both JAK2 kinase activity and EpoR cytoplasmic tyrosines are important for ligand-dependent EpoR internalization. Phosphorylated Y429, Y431, and Y479 in the EpoR cytoplasmic domain bind p85 subunit of PI3 kinase on Epo stimulation and individually are sufficient to mediate Epo-dependent EpoR internalization. Knockdown of p85alpha and p85beta or expression of their dominant-negative forms, but not inhibition of PI3 kinase activity, dramatically impaired EpoR internalization, indicating that p85alpha and p85beta may recruit proteins in the endocytic machinery on Epo stimulation. Furthermore, mutated EpoRs from primary familial and congenital polycythemia (PFCP) patients lacking the 3 important tyrosines do not bind p85 or internalize on stimulation. Addition of residues encompassing Y429 and Y431 to these truncated receptors restored p85beta binding and Epo sensitivity. Our results identify a novel PI3 kinase activity-independent function of p85 in EpoR internalization and support a model that defects of internalization in truncated EpoRs from PFCP patients contribute to Epo hypersensitivity and prolonged signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.