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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1888-1891. Prepublished online as a Blood First Edition Paper on October 27, 2005; DOI 10.1182/blood-2005-06-2304. This Article Full Text (PDF) All Versions of this Article: 2005-06-2304v1 107/5/1888    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 Ghaffari, S. Articles by Lodish, H. F Search for Related Content PubMed PubMed Citation Articles by Ghaffari, S. Articles by Lodish, H. F Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 9, 2005 Accepted October 19, 2005 AKT induces erythroid cell maturation of JAK2-deficient fetal liver progenitor cells and is required for epo regulation of erythroid cell differentiation Saghi Ghaffari*, Claire Kitidis, Wei Zhao, Dragan Marinkovic, Mark D Fleming, Biao Luo, Joseph Marszalek, and Harvey F Lodish Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY, USA; Department of Medicine, Division of Hematology Oncology, Mount Sinai School of Medicine, New York, NY, USA Whitehead Institute for Biomedical Research, Cambridge, MA, USA Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY, USA Department of Pathology, Children's Hospital Harvard Medical School, Boston, MA, USA Whitehead Institute for Biomedical Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA * Corresponding author; email: saghi.ghaffari{at}mssm.edu. AKT serine threonine kinase of protein kinase B (PKB) family plays essential roles in cell survival, growth, metabolism and differentiation. In the erythroid system, AKT is known to be rapidly phosphorylated and activated in response to Erythropoietin (Epo) engagement of Epo receptor (EpoR) and to sustain survival signals in cultured erythroid cells. Here we demonstrate that activated AKT complements EpoR signaling and supports erythroid cell differentiation in wild type and JAK2-deficient fetal liver cells. We show that erythroid maturation of AKT-transduced cells is not solely dependent on AKT-induced cell survival or proliferation signals suggesting that AKT transduces also a differentiation-specific signal downstream of EpoR in erythroid cells. Downregulation of expression of AKT kinase by RNA interference, or AKT activity by expression of dominant negative forms, inhibits significantly fetal liver-derived erythroid cell colony-formation and gene expression, demonstrating that AKT is required for Epo regulation of erythroid cell maturation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Maturation and enucleation of primitive erythroblasts during mouse embryogenesis is accompanied by changes in cell-surface antigen expression Stuart T. Fraser, Joan Isern, and Margaret H. Baron Blood 2007 109: 343-352. [Abstract] [Full Text] [PDF] This article has been cited by other articles: I. V. Libani, E. C. Guy, L. Melchiori, R. Schiro, P. Ramos, L. Breda, T. Scholzen, A. Chadburn, Y. Liu, M. Kernbach, et al. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in {beta}-thalassemia Blood, August 1, 2008; 112(3): 875 - 885. 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Wojchowski Erythropoietin modulation of podocalyxin and a proposed erythroblast niche Blood, July 15, 2007; 110(2): 509 - 518. [Abstract] [Full Text] [PDF] H. K. Bone and M. J. Welham Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis J. Cell Sci., May 15, 2007; 120(10): 1752 - 1762. [Abstract] [Full Text] [PDF] P. Rimmele, O. Kosmider, P. Mayeux, F. Moreau-Gachelin, and C. Guillouf Spi-1/PU.1 participates in erythroleukemogenesis by inhibiting apoptosis in cooperation with Epo signaling and by blocking erythroid differentiation Blood, April 1, 2007; 109(7): 3007 - 3014. [Abstract] [Full Text] [PDF] S. T. Fraser, J. Isern, and M. H. Baron Maturation and enucleation of primitive erythroblasts during mouse embryogenesis is accompanied by changes in cell-surface antigen expression Blood, January 1, 2007; 109(1): 343 - 352. [Abstract] [Full Text] [PDF] T. G.P. Bumm, C. Elsea, A. S. Corbin, M. Loriaux, D. Sherbenou, L. Wood, J. Deininger, R. T. 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