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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 Henry, M. K. Articles by Quelle, F. W. Search for Related Content PubMed PubMed Citation Articles by Henry, M. K. Articles by Quelle, F. W. Related Collections Neoplasia Cell Cycle Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2001, Vol. 98, No. 3, pp. 834-841 NEOPLASIA DNA damage-induced cell-cycle arrest of hematopoietic cells is overridden by activation of the PI-3 kinase/Akt signaling pathway Matthew K. Henry, Jeffrey T. Lynch, Alex K. Eapen, and Frederick W. Quelle From the Department of Pharmacology and the Immunology Graduate Program, The University of Iowa College of Medicine, Iowa City. Exposure of hematopoietic cells to DNA-damaging agents induces cell-cycle arrest at G1 and G2/M checkpoints. Previously, it was shown that DNA damage-induced growth arrest of hematopoietic cells can be overridden by treatment with cytokine growth factors, such as erythropoietin (EPO) or interleukin-3 (IL-3). Here, the cytokine-activated signaling pathways required to override G1 and G2/M checkpoints induced by -irradiation (-IR) are characterized. Using factor-dependent myeloid cells stably expressing EPO receptor (EPO-R) mutants, it is shown that removal of a minimal domain required for PI-3K signaling abrogated the ability of EPO to override -IR-induced cell-cycle arrest. Similarly, the ability of cytokines to override -IR-induced arrest was abolished by an inhibitor of PI-3K (LY294002) or by overexpression of dominant-negative Akt. Moreover, the ability of EPO to override these checkpoints in cells expressing defective EPO-R mutants could be restored by overexpression of a constitutively active Akt. Thus, activation of a PI-3K/Akt signaling pathway is required for cytokine-dependent suppression of DNA-damage induced checkpoints. Together, these findings suggest a novel role for PI-3K/Akt pathways in the modulation of growth arrest responses to DNA damage in hematopoietic cells. © 2001 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: V. S. Tompkins, J. Hagen, A. A. Frazier, T. Lushnikova, M. P. Fitzgerald, A. di Tommaso, V. Ladeveze, F. E. Domann, C. M. Eischen, and D. E. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020