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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 12; pp. 4739 - 4744
• Main Authors: Jia, Yonghui, Loison, Fabien, Hattori, Hidenori, Li, Yitang, Erneux, Christophe, Park, Shin-Young, Gao, Chong, Chai, Li, Silberstein, Leslie E, Schurmans, Stephane, Luo, Hongbo R
• Format: Journal Article Web Resource
• Language: English
• Published: United States National Academy of Sciences 25.03.2008; National Acad Sciences
• Subjects: Animals; Apoptosis; B lymphocytes; Biochemistry; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Biological Sciences; Blood Cell Count; Bone marrow; Bone marrow cells; Cell Differentiation; Cell Division; Cell Proliferation; Gene Deletion; Genetics & genetic processes; Génétique & processus génétiques; Hematopoiesis; Inositol 1,4,5-Trisphosphate - metabolism; Inositol phosphate; Inositols; Kinases; Knockout mice; Leukocytes; Life sciences; Lymphocytes; Mice; Mice, Knockout; Myeloid Progenitor Cells - cytology; Myeloid Progenitor Cells - enzymology; Myelopoiesis - physiology; Neutrophils; Neutrophils - cytology; Neutrophils - enzymology; Phosphates; Phosphotransferases (Alcohol Group Acceptor) - deficiency; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Progenitor cells; Sciences du vivant; Signal Transduction; Stem cells; T cell receptors; T lymphocytes; Vitamin B
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0800218105

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 p21cip¹, one of the downstream targets of Akt, was augmented, which can lead to the suppression of the cell cycle-inhibitory effect of p21.