Inositol 1,3,4,5-tetrakisphosphate is essential for T lymphocyte development

Abstract

Inositol 1,4,5-trisphosphate (Ins(1,4,5)P₃) is phosphorylated by Ins(1,4,5)P₃ 3-kinase, generating inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P₄). The physiological function of Ins(1,3,4,5)P₄ is still unclear, but it has been reported to be a potential modulator of calcium mobilization. Disruption of the gene encoding the ubiquitously expressed Ins(1,4,5)P₃ 3-kinase isoform B (Itpkb) in mice caused a severe T cell deficiency due to major alterations in thymocyte responsiveness and selection. However, we were unable to detect substantial defects in Ins(1,4,5)P₃ amounts or calcium mobilization in Itpkb^−/− thymocytes. These data indicate that Itpkb and Ins(1,3,4,5)P₄ define an essential signaling pathway for T cell precursor responsiveness and development.