ORBi: Maréchal Y. - Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells.

Reference : Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and surviva...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology Life sciences : Genetics & genetic processes
	To cite this reference:	http://hdl.handle.net/2268/8820

Title :	Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells.
Language :	English
Author, co-author :	Maréchal, Y. [Université Libre de Bruxelles - ULB > > > >]
	Pesesse, X. [Université Libre de Bruxelles - ULB > > > >]
	Jia, Y. [Université Libre de Bruxelles - ULB > > > >]
	Pouillon, V. [Université Libre de Bruxelles - ULB > > > >]
	Pérez-Morga, D. [Université Libre de Bruxelles - ULB > > > >]
	Daniel, J. [Université Libre de Bruxelles - ULB > > > >]
	Izui, S. [Centre Médical Universitaire, Faculté de Médecine, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland > > > >]
	Cullen, P. J. [University of Bristol, Bristol BS8 1TD, United Kingdom > > > >]
	Leo, O. [Université Libre de Bruxelles - ULB > > > >]
	Luo, H. R. [Université Libre de Bruxelles - ULB > > > >]
	Erneux, C. [Université Libre de Bruxelles - ULB > > > >]
	Schurmans, Stéphane [Université Libre de Bruxelles - ULB > Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire > > >]
Publication date :	2007
Journal title :	Proceedings of the National Academy of Sciences of the United States of America
Publisher :	National Academy of Sciences
Volume :	104
Pages :	13978-13983
Peer reviewed :	Yes (verified by ORBi)
Audience :	International
ISSN :	0027-8424
e-ISSN :	1091-6490
City :	Washington
Country :	DC
Keywords :	[en] apoptosis ; inositol phosphate ; lymphocyte ; Rasa3
Abstract :	[en] 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
Target :	Researchers ; Professionals
Permalink :	http://hdl.handle.net/2268/8820
DOI :	10.1073/pnas.0704312104

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