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Blood, 29 January 2009, Vol. 113, No. 5, pp. 1037-1044. Prepublished online as a Blood First Edition Paper on October 16, 2008; DOI 10.1182/blood-2008-06-163725. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-06-163725v1 113/5/1037    most recent 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Matsuda, S. Articles by Koyasu, S. Search for Related Content PubMed PubMed Citation Articles by Matsuda, S. Articles by Koyasu, S. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Critical role of class IA PI3K for c-Rel expression in B lymphocytes Satoshi Matsuda1,2, Yohei Mikami1, Masashi Ohtani1,2, Mari Fujiwara1,2, Yasuko Hirata1,2, Akiko Minowa1,2, Yasuo Terauchi2,3, Takashi Kadowaki2,3, and Shigeo Koyasu1,2 1 Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo; 2 Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo; and 3 Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan The fact that the Xid mutation of Btk impairs the ability of pleckstrin homo-logy domain of Btk to bind phosphatidylinositol-(3,4,5)-trisphosphate, a product of class IA phosphoinositide-3 kinases (PI3Ks), has been considered strong evidence for the hypothesis that Btk functions downstream of PI3Ks. We demonstrate here that the Xid mutation renders the Btk protein unstable. Furthermore, class IA PI3K- and Btk-deficient mice show different phenotypes in B-cell development, collectively indicating that PI3Ks and Btk differentially function in BCR signal transduction. Nevertheless, both PI3K and Btk are required for the activation of NF-B, a critical transcription factor family for B-cell development and function. We demonstrate that PI3Ks maintain the expression of NF-B proteins, whereas Btk is known to be essential for IB degradation and the translocation of NF-B to the nucleus. The loss of PI3K activity results in marked reduction of c-Rel and to a lesser extent RelA expression. The lentivirus-mediated introduction of c-Rel corrects both developmental and proliferative defects in response to BCR stimulation in class IA PI3K-deficient B cells. These results show that the PI3K-mediated control of c-Rel expression is essential for B-cell functions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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