Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis

[en] Inositol trisphosphate 3-kinase B (InsP3KB) belongs to a family of kinases that convert inositol 1,4,5-trisphosphate (Ins(1,4,5)P3 or IP3) to inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4). Previous studies have shown that disruption of InsP3KB leads to impaired T cell and B cell development as well as hyperactivation of neutrophils. Here, we demonstrate that InsP3KB is also a physiological modulator of myelopoiesis. The InsP3KB gene is expressed in all hematopoietic stem/progenitor cell populations. In InsP3KB null mice, the bone marrow granulocyte monocyte progenitor (GMP) population was expanded, and GMP cells proliferated significantly faster. Consequently, neutrophil production in the bone marrow was enhanced, and the peripheral blood neutrophil count was also substantially elevated in these mice. These effects might be due to enhancement of PtdIns(3,4,5)P3/Akt signaling in the InsP3KB null cells. Phosphorylation of cell cycle-inhibitory protein p21(cip1), one of the downstream targets of Akt, was augmented, which can lead to the suppression of the cell cycle-inhibitory effect of p21

Disciplines :

Biochemistry, biophysics & molecular biology
Genetics & genetic processes

Author, co-author :

Jia, Y.; Joint Program in Transfusion Medicine, Harvard Medical School, Boston, MA 02115

Loison, F.; Joint Program in Transfusion Medicine, Harvard Medical School, Boston, MA 02115

Erneux, C.; Université Libre de Bruxelles - ULB

Park, S.; Joint Program in Transfusion Medicine, Harvard Medical School, Boston, MA 02115

Gao, C.; Joint Program in Transfusion Medicine, Harvard Medical School, Boston, MA 02115

Chai, L.; Joint Program in Transfusion Medicine, Harvard Medical School, Boston, MA 02115

Silberstein, L. E.; Joint Program in Transfusion Medicine, Harvard Medical School, Boston, MA 02115

Schurmans, Stéphane ; Université Libre de Bruxelles - ULB > Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire

Luo, H. R.; Joint Program in Transfusion Medicine, Harvard Medical School, Boston, MA 02115

Language :

English

Title :

Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis

Publication date :

2008

Journal title :

Proceedings of the National Academy of Sciences of the United States of America

ISSN :

0027-8424

eISSN :

1091-6490

Publisher :

National Academy of Sciences, Washington, United States - District of Columbia

Volume :

105

Pages :

4739-4744

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 04 January 2010

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