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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3147-3153. Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-01-0078. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0078v1 102/9/3147    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Li, K. Articles by Wojchowski, D. M. Search for Related Content PubMed PubMed Citation Articles by Li, K. Articles by Wojchowski, D. M. Related Collections Hematopoiesis and Stem Cells Red Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Attenuated signaling by a phosphotyrosine-null Epo receptor form in primary erythroid progenitor cells Ke Li, Madhu P. Menon, Vinit G. Karur, Shailaja Hegde, and Don M. Wojchowski From the Immunobiology Program and Department of Veterinary Science, The Pennsylvania State University, University Park, PA. Signals provided by the erythropoieitin receptor (EpoR) are required for erythroid development beyond the erythroid colony-forming unit (CFU-e) stage and are propagated via the EpoR-tethered Janus kinase, JAK2. JAK2 functions, in part, to phosphorylate 8 conserved EpoR phosphotyrosine (PY) sites for the binding of a diverse set of signaling factors. However, recent studies in transgenic and knock-in mice have demonstrated substantial bioactivity for PY-null EpoR forms. Presently, the activities of a PY-null EpoR-HM form in primary progenitor cells from knock-in mice were further assessed using optimized Epo dose-dependent proliferation, survival, and differentiation assays. As compared with the wild-type (wt)–EpoR, EpoR-HM activity was compromised several-fold in each context when Epo was limited to physiologic concentrations. Possible compensatory increases in serum growth factor levels also were investigated, and as assayed using embryonic stem (ES) cell–derived erythroid G1E2 cells, activities in serum from EpoR-HM mice were substantially elevated. In addition, when challenged with phenylhydrazine-induced anemia, EpoR-HM mice failed to respond with efficient splenic stress erythropoiesis. Thus, the function of this JAK2-coupled but minimal PY-null EpoR-HM form appears to be attenuated in several contexts and to be assisted in vivo by compensatory mechanisms. Roles normally played by EpoR PY sites and distal domains therefore should receive continued attention. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Fang, M. Menon, W. Kapelle, O. Bogacheva, O. Bogachev, E. Houde, S. Browne, P. Sathyanarayana, and D. M. Wojchowski EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone marrow erythroblasts Blood, October 1, 2007; 110(7): 2361 - 2370. [Abstract] [Full Text] [PDF] P. Sathyanarayana, M. P. Menon, O. Bogacheva, O. Bogachev, K. Niss, W. S. Kapelle, E. Houde, J. Fang, and D. M. Wojchowski Erythropoietin modulation of podocalyxin and a proposed erythroblast niche Blood, July 15, 2007; 110(2): 509 - 518. [Abstract] [Full Text] [PDF] M. Suzuki, K. Ohneda, S. Hosoya-Ohmura, S. Tsukamoto, O. Ohneda, S. Philipsen, and M. Yamamoto Real-time monitoring of stress erythropoiesis in vivo using Gata1 and beta-globin LCR luciferase transgenic mice Blood, July 15, 2006; 108(2): 726 - 733. [Abstract] [Full Text] [PDF] T. Buchse, H. Prietzsch, T. Sasse, S. Korbel, G. Stigge, S. Bogdanow, J. Brock, and T. Bittorf Profiling of Early Gene Expression Induced by Erythropoietin Receptor Structural Variants J. Biol. Chem., March 24, 2006; 281(12): 7697 - 7707. [Abstract] [Full Text] [PDF] T. Montoye, I. Lemmens, D. Catteeuw, S. Eyckerman, and J. Tavernier A systematic scan of interactions with tyrosine motifs in the erythropoietin receptor using a mammalian 2-hybrid approach Blood, June 1, 2005; 105(11): 4264 - 4271. [Abstract] [Full Text] [PDF]

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