Critical role of class IA PI3K for c-Rel expression in B lymphocytes

Satoshi Matsuda, Yohei Mikami, Masashi Ohtani, Mari Fujiwara, Yasuko Hirata, Akiko Minowa, Yasuo Terauchi, Takashi Kadowaki, Shigeo Koyasu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The fact that the Xid mutation of Btk impairs the ability of pleckstrin homology 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 -KB, a critical transcription factor family for B-cell development and function. We demonstrate that PI3Ks maintain the expression of NF -KB proteins, whereas Btk is known to be essential for I -KB degradation and the translocation of NF -KB 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 PI3Kdeficient B cells. These results show that the PI3K-mediated control of c-Rel expression is essential for B-cell functions.

Original languageEnglish
Pages (from-to)1037-1044
Number of pages8
JournalBlood
Volume113
Issue number5
DOIs
Publication statusPublished - 2009 Jan 29

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Critical role of class IA PI3K for c-Rel expression in B lymphocytes'. Together they form a unique fingerprint.

  • Cite this

    Matsuda, S., Mikami, Y., Ohtani, M., Fujiwara, M., Hirata, Y., Minowa, A., Terauchi, Y., Kadowaki, T., & Koyasu, S. (2009). Critical role of class IA PI3K for c-Rel expression in B lymphocytes. Blood, 113(5), 1037-1044. https://doi.org/10.1182/blood-2008-06-163725