Phosphoinositide 3-kinases in immunity: Lessons from knockout mice

Phosphoinositide 3-kinases (PI3Ks) constitute a family of evolutionarily conserved lipid kinases that phosphorylate the D3 position of the inositol ring of phosphoinositides and produce PI(3)P, PI(3,4)P-2, and PI(3,4,5)P-3. Intense in vitro research over the last decade has unequivocally demonstrated that PI3Ks, in particular those belonging to class 1, regulate a vast array of fundamental cellular responses. Given the pleiotropic roles of PI3Ks and the lipid product PI(3,4,5)P-3 in plethora of cellular responses, it is pertinent to explore the significance of PI3K signaling in vivo. In the past two or three years, the components of this signaling pathway have been genetically manipulated in mouse. This review briefly summarizes the immunological significance of PI3K signaling as revealed by the study of gene-targeted "knockout" mice.