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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1461-1468. Prepublished online as a Blood First Edition Paper on May 16, 2006; DOI 10.1182/blood-2006-03-014209. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2006-03-014209v1 108/5/1461    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 Ekert, P. G Articles by Vaux, D. L Search for Related Content PubMed PubMed Citation Articles by Ekert, P. G Articles by Vaux, D. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 14, 2005 Accepted April 28, 2006 Cell death provoked by loss of Interleukin-3 signalling is independent of Bad, Bim, and PI3 Kinase, but depends in part on Puma Paul G Ekert*, Anissa M Jabbour, Anand Manoharan, Jacki E Heraud, Jai Yu, Miha Pakusch, Ewa M Michalak, Priscilla N Kelly, Bernard Callus, Thomas Kieffer, Anne Verhagen, John Silke, Andreas Strasser, Christoph Borner, and David L Vaux Children's Cancer Centre, Murdoch Children's Research Institute, Royal Children's,Victoria,Australia Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University of Freiburg, Germany The Walter and Eliza Hall Institute for Medical Research, Victoria, Australia Department of Biochemistry, La Trobe University, Bundoora, Victoria, Australia * Corresponding author; email: paul.ekert{at}rch.org.au. Growth and survival of hematopoietic cells is regulated by growth factors and cytokines, such as interleukin 3 (IL-3). When cytokine is removed, cells dependent on IL- 3 kill themselves by a mechanism that is inhibited by over-expression of Bcl-2, and is likely to be mediated by pro-apoptotic Bcl-2 family members. Bad and Bim are two such BH3-only Bcl-2 family members that have been implicated as key initiators in apoptosis following growth factor withdrawal, particularly in IL-3 dependent cells. To test the role of Bad, Bim and other pro- apoptotic Bcl-2 family members in IL-3 withdrawal induced apoptosis, we generated IL-3 dependent cell lines from mice lacking the genes for Bad, Bim, Puma, both Bad and Bim, and both Bax and Bak. Surprisingly, Bad was not required for cell death following IL-3 withdrawal, suggesting changes to phosphorylation of Bad play only a minor role in apoptosis in this system. Deletion of Bim also had no effect, but cells lacking Puma survived and formed colonies when IL-3 was restored. PI3 kinase pathway inhibition promoted apoptosis in the presence or absence of IL-3, did not require Bad, Bim or Puma, suggesting IL-3 receptor survival signals and PI3 kinase survival signals are independent. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. P. Fortin, M. J. Ennis, B. A. Savitch, D. Carpentieri, W. S. McDonough, J. A. Winkles, J. C. Loftus, C. Kingsley, G. Hostetter, and N. L. Tran Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Stimulation of Glioma Cell Survival Is Dependent on Akt2 Function Mol. Cancer Res., November 1, 2009; 7(11): 1871 - 1881. [Abstract] [Full Text] [PDF] T. R. Hercus, D. Thomas, M. A. Guthridge, P. G. Ekert, J. King-Scott, M. W. Parker, and A. F. 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Strasser, and G. Nilsson The BH3-only protein Puma plays an essential role in cytokine deprivation induced apoptosis of mast cells Blood, November 1, 2007; 110(9): 3209 - 3217. [Abstract] [Full Text] [PDF] J. Pardo, C. Urban, E. M. Galvez, P. G. Ekert, U. Muller, J. Kwon-Chung, M. Lobigs, A. Mullbacher, R. Wallich, C. Borner, et al. The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice J. Cell Biol., August 14, 2006; 174(4): 509 - 519. [Abstract] [Full Text] [PDF]

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