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Blood, 1 August 2004, Vol. 104, No. 3, pp. 784-787. Prepublished online as a Blood First Edition Paper on April 6, 2004; DOI 10.1182/blood-2003-09-3071. This Article Full Text (PDF) All Versions of this Article: 2003-09-3071v1 104/3/784    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 Yusuf, I. Articles by Fruman, D. A Search for Related Content PubMed PubMed Citation Articles by Yusuf, I. Articles by Fruman, D. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 8, 2003 Accepted March 23, 2004 Optimal B cell proliferation requires phosphoinositide 3-kinase-dependent inactivation of FOXO transcription factors Isharat Yusuf, Xiaocui Zhu, Michael G Kharas, Jing Chen, and David A Fruman* Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA Division of Biology, California Institute of Technology, Pasadena, CA, USA * Corresponding author; email: dfruman{at}uci.edu. Transcription factors of the Forkhead Box, class O (FOXO) family promote cell cycle arrest and/or apoptosis in a variety of cell types1,2. Mitogenic stimuli inactivate FOXO function via an evolutionarily conserved pathway involving the activation of phosphoinositide 3-kinase (PI3K) and its downstream effector, Akt. Although PI3K activation is required for B lymphocyte proliferation, it is not known whether PI3K-dependent inactivation of FOXO proteins is important for cell cycle progression and survival of these cells. Here we show that B cell receptor (BCR) engagement triggers PI3K-dependent phosphorylation and nuclear export of FOXO1. Furthermore, forced expression of PI3K-independent variants of FOXO1 or FOXO3a in activated B cells induces partial arrest in G1 phase of the cell cycle and increases apoptosis. These findings establish that FOXO inactivation is a functionally important consequence of PI3K signaling in primary B cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. M. Hinman, W. A. Nichols, T. M. Diaz, T. D. Gallardo, D. H. Castrillon, and A. B. Satterthwaite Foxo3-/- mice demonstrate reduced numbers of pre-B and recirculating B cells but normal splenic B cell sub-population distribution Int. 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Unterman, A. Trautmann, and G. Bismuth Stable Activation of Phosphatidylinositol 3-Kinase in the T Cell Immunological Synapse Stimulates Akt Signaling to FoxO1 Nuclear Exclusion and Cell Growth Control J. Immunol., April 1, 2005; 174(7): 4161 - 4171. [Abstract] [Full Text] [PDF]

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