Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis.
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.
Jia
Yonghui
Y
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.
Loison
Fabien
F
Hattori
Hidenori
H
Li
Yitang
Y
Erneux
Christophe
C
Park
Shin-Young
SY
Gao
Chong
C
Chai
Li
L
Silberstein
Leslie E
LE
Schurmans
Stephane
S
Luo
Hongbo R
HR
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
D015544:Inositol 1,4,5-Trisphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase