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This Article Full Text Full Text (PDF) 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 Miller, C. P. Articles by Wojchowski, D. M. Search for Related Content PubMed PubMed Citation Articles by Miller, C. P. Articles by Wojchowski, D. M. Related Collections Hematopoiesis and Stem Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 February 2002, Vol. 99, No. 3, pp. 898-904 HEMATOPOIESIS Erythropoietin receptor-dependent erythroid colony-forming unit development: capacities of Y343 and phosphotyrosine-null receptor forms Chris P. Miller, Destin W. Heilman, and Don M. Wojchowski From the Department of Veterinary Science and the Programs in Immunobiology and Genetics, Pennsylvania State University, University Park. Red cell development depends on the binding of erythropoietin (EPO) to receptors expressed by erythroid colony-forming units (CFUe) and the subsequent activation of receptor-bound Janus kinase (Jak2). Jak2 then mediates the phosphorylation of receptor tyrosine sites and the recruitment of 25 or more Src homology 2 domain-encoding proteins and associated factors. Previous studies have shown that an EPO receptor form containing Jak2-binding domains plus a single phosphotyrosine343 (PY343)-STAT5-binding site provides all signals needed for erythroid cell development. However, roles for PY343 and STAT5 remain controversial, and findings regarding PY-null receptor activities and erythropoiesis in STAT5-deficient mice are disparate. To study activities of a PY-null EPO receptor in primary cells while avoiding compensatory mechanisms, a form retaining domains for Jak2 binding and activation, but lacking all cytoplasmic tyrosine sites, was expressed in transgenic mice from a GATA1 gene-derived vector as a human epidermal growth factor receptor- murine EPO receptor chimera (EE-T-Y343F). The bio-signaling capacities of this receptor form were investigated in CFUe from thiamphenicol-treated mice. Interestingly, this PY-null EPO receptor form supported CFUe development (in the absence of detectable STAT5 activation) at efficiencies within 3-fold of those levels mediated by either an EE-T-Y343 form or the endogenous EPO receptor. However, EE-T-Y343F-dependent Ter119+ erythroblast maturation was attenuated. In tests of cosignaling with c-Kit, EE-T-Y343F nonetheless retained full capacity to synergize with c-Kit in promoting erythroid progenitor cell proliferation. Thus, EPO receptor PY-dependent events can assist late erythropoiesis but may be nonessential for EPO receptor-c-Kit synergy. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N Robinson, S Giraud, C Saudan, N Baume, L Avois, P Mangin, and M Saugy Erythropoietin and blood doping Br. J. Sports Med., July 1, 2006; 40(suppl_1): i30 - i34. [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] X. Chu, Q. Tong, J. Y. Cheung, J. Wozney, K. Conrad, V. Mazack, W. Zhang, R. Stahl, D. L. Barber, and B. A. Miller Interaction of TRPC2 and TRPC6 in Erythropoietin Modulation of Calcium Influx J. Biol. Chem., March 12, 2004; 279(11): 10514 - 10522. [Abstract] [Full Text] [PDF] K. Li, M. P. Menon, V. G. Karur, S. Hegde, and D. M. Wojchowski Attenuated signaling by a phosphotyrosine-null Epo receptor form in primary erythroid progenitor cells Blood, November 1, 2003; 102(9): 3147 - 3153. [Abstract] [Full Text] [PDF] K. Li, C. Miller, S. Hegde, and D. Wojchowski Roles for an Epo Receptor Tyr-343 Stat5 Pathway in Proliferative Co-signaling with Kit J. Biol. Chem., October 17, 2003; 278(42): 40702 - 40709. [Abstract] [Full Text] [PDF] B. L. Tan, L. Hong, V. Munugalavadla, and R. Kapur Functional and Biochemical Consequences of Abrogating the Activation of Multiple Diverse Early Signaling Pathways in Kit. ROLE FOR Src KINASE PATHWAY IN KIT-INDUCED COOPERATION WITH ERYTHROPOIETIN RECEPTOR J. Biol. Chem., March 21, 2003; 278(13): 11686 - 11695. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020