title: Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis.
abstract: 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.
authors.affiliation: Department of Pathology, Dana-Farber/Harvard Cancer Center, Children's Hospital Boston and Joint Program in Transfusion Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Jia
authors.forename: Fabien
authors.initials: F
authors.lastname: Loison
authors.forename: Hidenori
authors.initials: H
authors.lastname: Hattori
authors.forename: Yitang
authors.initials: Y
authors.lastname: Li
authors.forename: Christophe
authors.initials: C
authors.lastname: Erneux
authors.forename: Shin-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Chong
authors.initials: C
authors.lastname: Gao
authors.forename: Li
authors.initials: L
authors.lastname: Chai
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Silberstein
authors.forename: Stephane
authors.initials: S
authors.lastname: Schurmans
authors.forename: Hongbo R
authors.initials: HR
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001772:Blood Cell Count; D002454:Cell Differentiation; D002455:Cell Division; D049109:Cell Proliferation; D017353:Gene Deletion; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000201:enzymology; D038042:Myelopoiesis / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015544:Inositol 1,4,5-Trisphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase