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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4457-4465. Prepublished online as a Blood First Edition Paper on February 24, 2004; DOI 10.1182/blood-2003-08-2713. This Article Full Text (PDF) All Versions of this Article: 2003-08-2713v1 103/12/4457    most recent Alert me when this article is cited Alert me if a correction is posted 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 van den Akker, E. Articles by von Lindern, M. Search for Related Content PubMed PubMed Citation Articles by van den Akker, E. Articles by von Lindern, M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted August 8, 2003 Accepted February 4, 2004 The tyrosine kinase receptor RON functions downstream the erythropoietin receptor to induce expansion of erythroid progenitors Emile van den Akker, Thamar van Dijk, Martine Parren-van Amelsvoort, Katja S Grossmann, Ute Schaeper, Kenya Toney-Earley, Susan E Waltz, Bob Lowenberg, and Marieke von Lindern* Hematology, Erasmus MC, Rotterdam, The Netherlands Max Delbruck Center, Berlin, Germany Surgery, University of Cincinnati College of Medicin, Cincinnati, OH, USA * Corresponding author; email: m.vonlindern{at}erasmusmmc.nl. Erythropoietin (Epo) is required for cell survival during differentiation and for progenitor expansion during stress erythropoiesis. While signaling pathways may couple directly to docking sites on the Epo-receptor, additional docking molecules expand the signaling platform of the receptor. We studied the role of the docking molecules Gab1 and Gab2 in Epo-induced signal transduction and erythropoiesis. Inhibitors of phosphatidylinositide-3-kinase and Src-kinases suppressed Epo-dependent phosphorylation of Gab2. In contrast, Gab1 activation is dependent on recruitment and phosphorylation by the tyrosine kinase receptor RON, with which it is constitutively associated. Activation of RON induces phosphorylation of Gab1, MAPK and PKB, but not Stat5. Activation of RON was sufficient to replace Epo in progenitor expansion, but not in differentiation. In conclusion, we elucidated a novel mechanism specifically involved in expansion of erythroblasts, involving RON as a downstream target of the EpoR. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Erythroblast renewal: new roles for RON and Gab1 in EpoR signaling Hartmut Beug Blood 2004 103: 4376-4377. [Full Text] [PDF] This article has been cited by other articles: P. Sathyanarayana, A. Dev, J. Fang, E. Houde, O. Bogacheva, O. Bogachev, M. Menon, S. Browne, A. Pradeep, C. Emerson, et al. EPO receptor circuits for primary erythroblast survival Blood, June 1, 2008; 111(11): 5390 - 5399. [Abstract] [Full Text] [PDF] W. J. Bakker, T. B. van Dijk, M. Parren-van Amelsvoort, A. Kolbus, K. Yamamoto, P. Steinlein, R. G. W. Verhaak, T. W. Mak, H. Beug, B. Lowenberg, et al. Differential Regulation of Foxo3a Target Genes in Erythropoiesis Mol. Cell. Biol., May 15, 2007; 27(10): 3839 - 3854. [Abstract] [Full Text] [PDF] M. P. Menon, J. Fang, and D. M. Wojchowski Core erythropoietin receptor signals for late erythroblast development Blood, April 1, 2006; 107(7): 2662 - 2672. [Abstract] [Full Text] [PDF] J. Zhang, M. S. Randall, M. R. Loyd, W. Li, R. L. Schweers, D. A. Persons, J. E. Rehg, C. T. Noguchi, J. N. Ihle, and P. A. Ney Role of erythropoietin receptor signaling in Friend virus-induced erythroblastosis and polycythemia Blood, January 1, 2006; 107(1): 73 - 78. [Abstract] [Full Text] [PDF] X. Wei, L. Hao, S. Ni, Q. Liu, J. Xu, and P. H. Correll Altered Exon Usage in the Juxtamembrane Domain of Mouse and Human RON Regulates Receptor Activity and Signaling Specificity J. Biol. Chem., December 2, 2005; 280(48): 40241 - 40251. [Abstract] [Full Text] [PDF] E. van den Akker, S. Ano, H.-M. Shih, L.-C. Wang, M. Pironin, J. J. Palvimo, N. Kotaja, O. Kirsh, A. Dejean, and J. Ghysdael FLI-1 Functionally Interacts with PIASx{alpha}, a Member of the PIAS E3 SUMO Ligase Family J. Biol. Chem., November 11, 2005; 280(45): 38035 - 38046. [Abstract] [Full Text] [PDF] K. Nishigaki, C. Hanson, T. Jelacic, D. Thompson, and S. Ruscetti Friend spleen focus-forming virus transforms rodent fibroblasts in cooperation with a short form of the receptor tyrosine kinase Stk PNAS, October 25, 2005; 102(43): 15488 - 15493. [Abstract] [Full Text] [PDF] X. Wei, S. Ni, and P. H. Correll Uncoupling Ligand-dependent and -independent Mechanisms for Mitogen-activated Protein Kinase Activation by the Murine Ron Receptor Tyrosine Kinase J. Biol. Chem., October 21, 2005; 280(42): 35098 - 35107. [Abstract] [Full Text] [PDF] M. Blazquez-Domingo, G. Grech, and M. von Lindern Translation Initiation Factor 4E Inhibits Differentiation of Erythroid Progenitors Mol. Cell. Biol., October 1, 2005; 25(19): 8496 - 8506. [Abstract] [Full Text] [PDF]

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