Genomes and Genes
Gene Symbol: erythropoietin receptor
Description: erythropoietin receptor
Alias: EPO-R, erythropoietin receptor
Products: erythropoietin receptor
- Kumar S, Zhang G, Bastian B, Arcasoy M, Karande P, Pushparajan A, et al. Erythropoietin receptor contributes to melanoma cell survival in vivo. Oncogene. 2012;31:1649-60 pubmed publisher..These data support that EpoR is functional in melanoma and EpoR activation may promote melanoma progression, and suggest that Epo may stimulate angiogenesis and increase survival of melanoma cells under hypoxic condition in vivo. ..
- Arcasoy M, Karayal A. Erythropoietin hypersensitivity in primary familial and congenital polycythemia: role of tyrosines Y285 and Y344 in erythropoietin receptor cytoplasmic domain. Biochim Biophys Acta. 2005;1740:17-28 pubmedb>Erythropoietin receptor (EPOR) gene mutations leading to truncations of the cytoplasmic, carboxy-terminal region of EPOR have been described in some patients with primary familial and congenital polycythemia (PFCP), a disorder ..
- Arcasoy M, Jiang X, Haroon Z. Expression of erythropoietin receptor splice variants in human cancer. Biochem Biophys Res Commun. 2003;307:999-1007 pubmed..These findings indicate the expression of multiple EPOR isoforms in human cancer cells that may modulate the cellular effects of recombinant human EPO or EPO-EPOR antagonists. ..
- Pircher T, Geiger J, Zhang D, Miller C, Gaines P, Wojchowski D. Integrative signaling by minimal erythropoietin receptor forms and c-Kit. J Biol Chem. 2001;276:8995-9002 pubmed..Thus, integration circuits exist in only select downstream pathways within Epo and stem call factor receptor signaling. ..
- Chin K, Yu X, Beleslin Cokic B, Liu C, Shen K, Mohrenweiser H, et al. Production and processing of erythropoietin receptor transcripts in brain. Brain Res Mol Brain Res. 2000;81:29-42 pubmedThe expression of erythropoietin receptor (EpoR) in brain and neuronal cells, and hypoxia-responsive production of erythropoietin (Epo) in the brain suggests that the function of Epo as a survival or viability factor may extend beyond ..
- Kralovics R, Indrak K, Stopka T, Berman B, Prchal J, Prchal J. Two new EPO receptor mutations: truncated EPO receptors are most frequently associated with primary familial and congenital polycythemias. Blood. 1997;90:2057-61 pubmed..So far, most of the described EPOR mutations (6 out of 8) associated with PFCP result in an absence of the C-terminal negative regulatory domain of the receptor. ..
- Winkelmann J, Penny L, Deaven L, Forget B, Jenkins R. The gene for the human erythropoietin receptor: analysis of the coding sequence and assignment to chromosome 19p. Blood. 1990;76:24-30 pubmedThe full-length coding sequence of the human erythropoietin receptor has been assembled from cDNA and genomic DNA...
- Brines M, Ghezzi P, Keenan S, Agnello D, de Lanerolle N, Cerami C, et al. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A. 2000;97:10526-31 pubmed..Given r-Hu-EPO's excellent safety profile, clinical trials evaluating systemically administered r-Hu-EPO as a general neuroprotective treatment are warranted. ..
- de la Chapelle A, Träskelin A, Juvonen E. Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis. Proc Natl Acad Sci U S A. 1993;90:4495-9 pubmed..Its effect is mediated by the erythropoietin receptor (EPOR), a member of a large family of cytokine receptors...
- Sasaki A, Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A. CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2. J Biol Chem. 2000;275:29338-47 pubmed..These data demonstrate that binding of CIS3 to the EPOR augments the inhibitory effect of CIS3. CIS3 binding to both EPOR and JAK2 may explain a specific regulatory role of CIS3 in erythropoiesis. ..
- Witthuhn B, Quelle F, Silvennoinen O, Yi T, Tang B, Miura O, et al. JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell. 1993;74:227-36 pubmed..The results support the hypothesis that JAK2 is the kinase that couples EPO binding to tyrosine phosphorylation and mitogenesis. ..
- Acs G, Xu X, Chu C, Acs P, Verma A. Prognostic significance of erythropoietin expression in human endometrial carcinoma. Cancer. 2004;100:2376-86 pubmed..Increased Epo expression in endometrial carcinomas may be an independent prognostic and/or predictive factor. ..
- Fu P, Jiang X, Arcasoy M. Constitutively active erythropoietin receptor expression in breast cancer cells promotes cellular proliferation and migration through a MAP-kinase dependent pathway. Biochem Biophys Res Commun. 2009;379:696-701 pubmed publisherThe role of erythropoietin receptor (EpoR) expression in tumor cells and the potential of EpoR-mediated signaling to contribute to cellular proliferation and invasiveness require further characterization...
- Sinclair A, Coxon A, McCaffery I, Kaufman S, Paweletz K, Liu L, et al. Functional erythropoietin receptor is undetectable in endothelial, cardiac, neuronal, and renal cells. Blood. 2010;115:4264-72 pubmed publisher..Taken together, our data challenge the notion of presence or function of EpoR on nonhematopoietic cells, and call into question the preclinical basis for clinical studies exploring direct, "pleiotropic" actions of ESAs. ..
- Swift S, Ellison A, Kassner P, McCaffery I, Rossi J, Sinclair A, et al. Absence of functional EpoR expression in human tumor cell lines. Blood. 2010;115:4254-63 pubmed publisher..These results conflict with the hypothesis that EpoR is functionally expressed in tumors. ..
- Todokoro K, Kuramochi S, Nagasawa T, Abe T, Ikawa Y. Isolation of a cDNA encoding a potential soluble receptor for human erythropoietin. Gene. 1991;106:283-4 pubmedAnalysis of human erythropoietin receptor-encoding cDNAs revealed the possible existence of a soluble receptor lacking the transmembrane and cytoplasmic domains.
- Jones S, D Andrea A, Haines L, Wong G. Human erythropoietin receptor: cloning, expression, and biologic characterization. Blood. 1990;76:31-5 pubmedWe have isolated the human homologue of the murine erythropoietin receptor (mEPO-R) from an erythroleukemia line, OCIM1, and from fetal liver. Both the cDNA and protein sequence of the human receptor were 82% homologous to the mEPO-R...
- Meyer L, Deau B, Forejtnikovà H, Dumenil D, Margottin Goguet F, Lacombe C, et al. beta-Trcp mediates ubiquitination and degradation of the erythropoietin receptor and controls cell proliferation. Blood. 2007;109:5215-22 pubmed
- Paragh G, Kumar S, Rakosy Z, Choi S, Xu X, Acs G. RNA interference-mediated inhibition of erythropoietin receptor expression suppresses tumor growth and invasiveness in A2780 human ovarian carcinoma cells. Am J Pathol. 2009;174:1504-14 pubmed publisher..Our findings suggest that EpoR may be constitutively active in some cancer cells in the absence of Epo and provide the first evidence for a potential role of an Epo-independent, EpoR-mediated pathway in the growth of some human cancers. ..
- Feldman L, Wang Y, Rhim J, Bhattacharya N, Loda M, Sytkowski A. Erythropoietin stimulates growth and STAT5 phosphorylation in human prostate epithelial and prostate cancer cells. Prostate. 2006;66:135-45 pubmed..These results have implications for our understanding of normal prostatic growth and development and of the pathobiology of human prostate cancer. ..
- Lee Y, Vortmeyer A, Lubensky I, Vogel T, Ikejiri B, Ferlicot S, et al. Coexpression of erythropoietin and erythropoietin receptor in von Hippel-Lindau disease-associated renal cysts and renal cell carcinoma. Clin Cancer Res. 2005;11:1059-64 pubmed..Such arrest may lead to autocrine stimulation, cell proliferation, and renal tumor development, similar to tumorigenesis of VHL disease-associated hemangioblastomas. ..
- Arcasoy M, Amin K, Chou S, Haroon Z, Varia M, Raleigh J. Erythropoietin and erythropoietin receptor expression in head and neck cancer: relationship to tumor hypoxia. Clin Cancer Res. 2005;11:20-7 pubmed..hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor [erythropoietin receptor (EPOR)]...
- Kralovics R, Sokol L, Prchal J. Absence of polycythemia in a child with a unique erythropoietin receptor mutation in a family with autosomal dominant primary polycythemia. J Clin Invest. 1998;102:124-9 pubmed..Failure of this child to develop polycythemia suggests the existence of as yet unidentified environmental or genetic factors that may suppress disease development. ..
- Nagai A, Nakagawa E, Choi H, Hatori K, Kobayashi S, Kim S. Erythropoietin and erythropoietin receptors in human CNS neurons, astrocytes, microglia, and oligodendrocytes grown in culture. J Neuropathol Exp Neurol. 2001;60:386-92 pubmed..These results suggest that proinflammatory cytokines regulate expression of EPO and EPOR in human neurons, astrocytes, and microglia and further facilitate interactions among different cell types in the human CNS. ..
- Motohashi T, Nakamura Y, Osawa M, Hiroyama T, Iwama A, Shibuya A, et al. Increased cell surface expression of C-terminal truncated erythropoietin receptors in polycythemia. Eur J Haematol. 2001;67:88-93 pubmed
- Huang L, Constantinescu S, Lodish H. The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor. Mol Cell. 2001;8:1327-38 pubmedWe show that Janus kinase 2 (JAK2), and more specifically just its intact N-terminal domain, binds to the erythropoietin receptor (EpoR) in the endoplasmic reticulum and promotes its cell surface expression...
- Nakamura Y, Komatsu N, Nakauchi H. A truncated erythropoietin receptor that fails to prevent programmed cell death of erythroid cells. Science. 1992;257:1138-41 pubmedA form of the human erythropoietin receptor (EPOR) was identified in which the cytoplasmic region is truncated by alternative splicing...
- Dagnon K, Pacary E, Commo F, Antoine M, Bernaudin M, Bernaudin J, et al. Expression of erythropoietin and erythropoietin receptor in non-small cell lung carcinomas. Clin Cancer Res. 2005;11:993-9 pubmed..Moreover, in the light of these results, the potential interactions between therapeutic recombinant Epo and the putative neoplastic Epo/Epo-R signaling pathways must be considered. ..
- Rundqvist H, Rullman E, Sundberg C, Fischer H, Eisleitner K, Ståhlberg M, et al. Activation of the erythropoietin receptor in human skeletal muscle. Eur J Endocrinol. 2009;161:427-34 pubmed publisherb>Erythropoietin receptor (EPOR) expression in non-hematological tissues has been shown to be activated by locally produced and/or systemically delivered EPO...
- Kirkeby A, van Beek J, Nielsen J, Leist M, Helboe L. Functional and immunochemical characterisation of different antibodies against the erythropoietin receptor. J Neurosci Methods. 2007;164:50-8 pubmed..Here, only the MAB307 antibody showed a partial effect at concentrations of 5-50 microg/ml. ..
- Arcasoy M, Amin K, Karayal A, Chou S, Raleigh J, Varia M, et al. Functional significance of erythropoietin receptor expression in breast cancer. Lab Invest. 2002;82:911-8 pubmed..These studies demonstrate the expression of functional receptors for EPO in breast cancer cells. ..
- Assaraf M, Diaz Z, Liberman A, Miller W, Arvanitakis Z, Li Y, et al. Brain erythropoietin receptor expression in Alzheimer disease and mild cognitive impairment. J Neuropathol Exp Neurol. 2007;66:389-98 pubmed..Erythropoietin (Epo) and the erythropoietin receptor (EpoR) are expressed in neural tissues and protect against oxidative and other stressors in various ..
- Blake T, Jenkins B, D Andrea R, Gonda T. Functional cross-talk between cytokine receptors revealed by activating mutations in the extracellular domain of the beta-subunit of the GM-CSF receptor. J Leukoc Biol. 2002;72:1246-55 pubmedSeveral reports have suggested an interaction between the erythropoietin receptor (EpoR) and the shared signaling subunit (hbeta(c)) of the human granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 ..
- Chin H, Arai A, Wakao H, Kamiyama R, Miyasaka N, Miura O. Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway. Blood. 1998;91:3734-45 pubmed..In addition, Lyn was demonstrated to phosphorylate the EpoR and Stat5 on tyrosines in vitro. These results suggest that Lyn may play a role in activation of the Jak2/Stat5 and other signaling pathways by the EpoR. ..
- Pelletier S, Gingras S, Funakoshi Tago M, Howell S, Ihle J. Two domains of the erythropoietin receptor are sufficient for Jak2 binding/activation and function. Mol Cell Biol. 2006;26:8527-38 pubmed..Collectively, the results suggest that Jak2 is the sole direct signaling molecule downstream of EpoR required for biological activity. ..
- Sokol L, Luhovy M, Guan Y, Prchal J, Semenza G, Prchal J. Primary familial polycythemia: a frameshift mutation in the erythropoietin receptor gene and increased sensitivity of erythroid progenitors to erythropoietin. Blood. 1995;86:15-22 pubmed..The transfected cells with another primary polycythemia associated EPOR mutant construct (G6002A) also exhibited increased sensitivity to EPO. ..
- Winter S, Shah K, Campo L, Turley H, Leek R, Corbridge R, et al. Relation of erythropoietin and erythropoietin receptor expression to hypoxia and anemia in head and neck squamous cell carcinoma. Clin Cancer Res. 2005;11:7614-20 pubmed..This study examines the protein and mRNA expression of erythropoietin and erythropoietin receptor in HNSCC and their relation to hypoxia, hemoglobin (Hb), and clinical outcome...
- Al Sheikh M, Mazurier E, Gardie B, Casadevall N, Galacteros F, Goossens M, et al. A study of 36 unrelated cases with pure erythrocytosis revealed three new mutations in the erythropoietin receptor gene. Haematologica. 2008;93:1072-5 pubmed publisherThirty-six unrelated cases with erythrocytosis of unknown origin were investigated. Exons 5-8 of the erythropoietin receptor gene (EPOR), the von Hippel-Lindau gene, and the prolyl hydroxylase domain protein 2 gene (PHD2) were screened ..
- Gong K, Zhang N, Zhang Z, Na Y. Coexpression of erythopoietin and erythopoietin receptor in sporadic clear cell renal cell carcinoma. Cancer Biol Ther. 2006;5:582-5 pubmed..Coexpression of Epo and EpoR was detected in 50 out of 54 tumors regardless of their VHL mutation status. The results suggest that coexpression of Epo and EpoR plays an important role in tumorigenesis of sporadic CCRCC. ..
- Beleslin Cokic B, Cokic V, Yu X, Weksler B, Schechter A, Noguchi C. Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cells. Blood. 2004;104:2073-80 pubmed..This effect of EPO on eNOS may be a physiologically relevant mechanism to counterbalance the hypertensive effects of increased hemoglobin-related NO destruction resulting from hypoxia-induced increased red cell mass. ..
- Walrafen P, Verdier F, Kadri Z, Chretien S, Lacombe C, Mayeux P. Both proteasomes and lysosomes degrade the activated erythropoietin receptor. Blood. 2005;105:600-8 pubmedActivation of the erythropoietin receptor (EpoR) after Epo binding is very transient because of the rapid activation of strong down-regulation mechanisms that quickly decrease Epo sensitivity of the cells...
- Vogel T, Brouwers F, Lubensky I, Vortmeyer A, Weil R, Walther M, et al. Differential expression of erythropoietin and its receptor in von hippel-lindau-associated and multiple endocrine neoplasia type 2-associated pheochromocytomas. J Clin Endocrinol Metab. 2005;90:3747-51 pubmed..These findings suggest an alternative process of tumorigenesis in VHL- and MEN 2-associated pheochromocytomas and implicate Epo as a clinical biomarker to differentiate these tumors. ..
- Luk C, Shi S, Choi D, Cai E, Schroer S, Woo M. In vivo knockdown of adipocyte erythropoietin receptor does not alter glucose or energy homeostasis. Endocrinology. 2013;154:3652-9 pubmed publisher..In contrast to the pharmacological effects of EPO, we demonstrate that EPO signaling at physiological levels is not essential for adipose tissue regulation of metabolism. ..
- Halupa A, Chohan M, Stickle N, Beattie B, Miller B, Barber D. Erythropoietin receptor Y479 couples to ERK1/2 activation via recruitment of phospholipase Cgamma. Exp Cell Res. 2005;309:1-11 pubmed..Hence, we have identified a novel adapter function for PLCgamma1 in EPO signaling in which recruitment of PLCgamma1 to EPO-R may lead to activation of the ERK pathway. ..
- Terraneo L, Samaja M. Comparative Response of Brain to Chronic Hypoxia and Hyperoxia. Int J Mol Sci. 2017;18: pubmed publisher..While for certain functions the expectation that hypoxia and hyperoxia should cause opposite responses is actually met, for others it is not, and both emerge as dangerous treatments. ..
- Schnöder T, Eberhardt J, Koehler M, Bierhoff H, Weinert S, Pandey A, et al. Cell autonomous expression of CXCL-10 in JAK2V617F-mutated MPN. J Cancer Res Clin Oncol. 2017;143:807-820 pubmed publisher..Our data provide first evidence for a link between oncogenic JAK2V617F signaling and cell intrinsic induction of CXCL10 induced by activated NFkB signaling. ..
- Menier C, Guillard C, Cassinat B, Carosella E, Rouas Freiss N. HLA-G turns off erythropoietin receptor signaling through JAK2 and JAK2 V617F dephosphorylation: clinical relevance in polycythemia vera. Leukemia. 2008;22:578-84 pubmed..of UT7/EPO and HEL erythroleukemia cells and characterized the mechanism by which HLA-G5 influences erythropoietin receptor (EPOR) signaling...
- Yokomizo R, Matsuzaki S, Uehara S, Murakami T, Yaegashi N, Okamura K. Erythropoietin and erythropoietin receptor expression in human endometrium throughout the menstrual cycle. Mol Hum Reprod. 2002;8:441-6 pubmed..In addition, we also hypothesize that ovarian steroids may stimulate Epo production in human endometrial glandular epithelial cells. ..
- Tauchi T, Feng G, Shen R, Hoatlin M, Bagby G, Kabat D, et al. Involvement of SH2-containing phosphotyrosine phosphatase Syp in erythropoietin receptor signal transduction pathways. J Biol Chem. 1995;270:5631-5 pubmed..These results suggest that Syp may be an important signaling component downstream of the EpoR and may regulate the proliferation and differentiation of hematopoietic cells. ..
- Yoshimura A, Lodish H. In vitro phosphorylation of the erythropoietin receptor and an associated protein, pp130. Mol Cell Biol. 1992;12:706-15 pubmed..Our data suggests that phosphorylation or interaction with a protein kinase in the carboxy-terminal region may down-modulate the proliferative action of the EPOR. ..
- Zhan H, Liu B, Reid S, Aoki K, Li C, Syed R, et al. Engineering a soluble extracellular erythropoietin receptor (EPObp) in Pichia pastoris to eliminate microheterogeneity, and its complex with erythropoietin. Protein Eng. 1999;12:505-13 pubmed..8 and 1.9 A respectively. (Form 1 and form 2 crystals were independently obtained at AxyS Pharmaceuticals, Inc. and Amgen, Inc. respectively.) Both contained one complex per asymmetric unit with a stoichiometry of two EPObps to one EPO. ..
- Tauchi T, Damen J, Toyama K, Feng G, Broxmeyer H, Krystal G. Tyrosine 425 within the activated erythropoietin receptor binds Syp, reduces the erythropoietin required for Syp tyrosine phosphorylation, and promotes mitogenesis. Blood. 1996;87:4495-501 pubmed..Moreover, Y425 in the EpoR reduces the Epo requirement for Syp tyrosine phosphorylation and promotes proliferation. ..
- Miao S, Wang S, Cheng X, Li Y, Zhang Q, Li G, et al. Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor. Cancer Cell Int. 2017;17:119 pubmed publisher..Several reports indicated that it could promote the tumor cell proliferation through its specific receptor (EPOR). Unfortunately, the role of EPO/EPOR in hepatocellular carcinoma (HCC) progressing is still uncertain...
- García Ramírez M, Hernandez C, Simo R. Expression of erythropoietin and its receptor in the human retina: a comparative study of diabetic and nondiabetic subjects. Diabetes Care. 2008;31:1189-94 pubmed publisher..At this early stage, other factors apart from hypoxia seem to be more important in accounting for the Epo upregulation that exists in the diabetic retina. ..
- Guillard C, Chretien S, Pelus A, Porteu F, Muller O, Mayeux P, et al. Activation of the mitogen-activated protein kinases Erk1/2 by erythropoietin receptor via a G(i )protein beta gamma-subunit-initiated pathway. J Biol Chem. 2003;278:11050-6 pubmed..This pathway is similar to the best characterized pathway used by seven transmembrane receptors coupled to G(i) to activate MAPK and may cooperate with other described Epo-dependent MAPK activation pathways in hematopoietic cells. ..