en
Scientific article
English

Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells

Publication date2007
Abstract

The contribution of the B isoform of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase (or Itpkb) and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P(4)], its reaction product, to B cell function and development remains unknown. Here, we show that mice deficient in Itpkb have defects in B cell survival leading to specific and intrinsic developmental alterations in the B cell lineage and antigen unresponsiveness in vivo. The decreased B cell survival is associated with a decreased phosphorylation of Erk1/2 and increased Bim gene expression. B cell survival, development, and antigen responsiveness are normalized in parallel to reduced expression of Bim in Itpkb(-/-) Bim(+/-) mice. Analysis of the signaling pathway downstream of Itpkb revealed that Ins(1,3,4,5)P(4) regulates subcellular distribution of Rasa3, a Ras GTPase-activating protein acting as an Ins(1,3,4,5)P(4) receptor. Together, our results indicate that Itpkb and Ins(1,3,4,5)P(4) mediate a survival signal in B cells via a Rasa3-Erk signaling pathway controlling proapoptotic Bim gene expression.

Keywords
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins/deficiency/*genetics
  • B-Lymphocyte Subsets/cytology/immunology/physiology
  • B-Lymphocytes/*cytology/immunology/*physiology
  • Bone Marrow/immunology
  • Cell Survival
  • Gene Expression Regulation
  • Immunoglobulin D/analysis
  • Immunoglobulin M/analysis
  • Inositol Phosphates/*pharmacology
  • Membrane Proteins/deficiency/*genetics
  • Mice
  • Mice, Knockout
  • Phosphotransferases (Alcohol Group Acceptor)/deficiency/*genetics
  • Proto-Oncogene Proteins/deficiency/*genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen/immunology
Affiliation Not a UNIGE publication
Citation (ISO format)
MARECHAL, Yoann et al. Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells. In: Proceedings of the National Academy of Sciences of the United States of America, 2007, vol. 104, n° 35, p. 13978–13983. doi: 10.1073/pnas.0704312104
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ISSN of the journal0027-8424
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