Role of phosphoinositide 3-kinase signaling in mast cells: new insights from knockout mouse studies.

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases essential for diverse physiological reactions. In recent years a series of gene-targeted mice lacking different types of PI3Ks and related molecules have been generated which enable us to understand the role of PI3K pathways, particularly class I members, in vivo. Analyses of such gene-targeted mice have led to major discoveries in the physiological roles of PI3K signaling in mast cell biology. In particular the role of PI3Ks has been extensively studied in signaling through the high-affinity IgE receptor (FcepsilonRI), since mast cells are the main effector cells in type I allergic reaction associated with IgE-dependent mechanisms. Furthermore, the knockout mice have provided significant information concerning the role of PI3K signals in mast cell differentiation. This review presents several new insights into mast cell biology, which have been elucidated by the analyses of these knockout mice.