{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:17:59Z","timestamp":1772137079529,"version":"3.50.1"},"reference-count":51,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,4,15]]},"abstract":"<jats:p>EPO (erythropoietin), the major hormone regulating erythropoiesis, functions via activation of its cell-surface receptor (EPO-R) present on erythroid progenitor cells. One of the most striking properties of EPO-R is its low expression on the cell surface, as opposed to its high intracellular levels. The low cell-surface expression of EPO-R may thus limit the efficacy of EPO that is routinely used to treat primary and secondary anaemia. In a recent study [Nahari, Barzilay, Hirschberg and Neumann (2008) Biochem. J. 410, 409\u2013416] we have shown that insertion of an NPVY sequence into the intracellular domain of EPO-R increases its cell-surface expression. In the present study we demonstrate that this NPVY EPO-R insert has a selective effect on EPO-mediated downstream signalling in Ba\/F3 cells expressing this receptor (NPVY-EPO-R). This is monitored by increased phosphorylation of the NPVY-EPO-R (on Tyr479), Akt, JAK2 (Janus kinase 2) and ERK1\/2 (extracellular-signal-regulated kinase 1\/2), but not STAT5 (signal transducer and activator of transcription 5), as compared with cells expressing wild-type EPO-R. This enhanced signalling is reflected in augmented proliferation at low EPO levels (0.05\u00a0units\/ml) and protection against etoposide-induced apoptosis. Increased cell-surface levels of NPVY-EPO-R are most probably not sufficient to mediate these effects as the A234E-EPO-R mutant that is expressed at high cell-surface levels does not confer an augmented response to EPO. Taken together, we demonstrate that insertion of an NPVY sequence into the cytosolic domain of the EPO-R confers not only improved maturation, but also selectively affects EPO-mediated signalling resulting in an improved responsiveness to EPO reflected in cell proliferation and protection against apoptosis.<\/jats:p>","DOI":"10.1042\/bj20091951","type":"journal-article","created":{"date-parts":[[2010,2,10]],"date-time":"2010-02-10T09:35:24Z","timestamp":1265794524000},"page":"305-312","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Insertion of an NPVY sequence into the cytosolic domain of the erythropoietin receptor selectively affects erythropoietin-mediated signalling and function"],"prefix":"10.1042","volume":"427","author":[{"given":"Tamar","family":"Liron","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tal","family":"Nahari","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam\u00a0C.","family":"Souroujon","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, The Open University of Israel, 1 University Road, P.O.B. 808, Raanana 43107, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drorit","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2010,3,29]]},"reference":[{"key":"2021112214291878700_B1","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1271\/bbb.64.1775","article-title":"Erythropoietin: multiple physiological functions and regulation of biosynthesis","volume":"64","author":"Sasaki","year":"2000","journal-title":"Biosci. 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