Emerging roles of phosphatidylinositol 3-monophosphate as a dynamic lipid second messenger

Abstract

The lipid products of phosphoinositide 3-kinase (PI3K) are involved in many cellular responses such as proliferation, migration and survival. Disregulation of PI3K-activated pathways is implicated in different disease including diabetes and cancer. Among the different products of PI3Ks, phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) has a well established role in signal transduction whereas the monophosphate phosphatidylinositol-3-phosphate (PtdIns-3-P) has been considered for a long time just a cellular component confined in endosomal structures. Only recently several evidence have indicated that PtdIns-3-P can also act as a dynamic intracellular second messenger. The role of PtdIns-3-P as mediator of crucial intracellular signals is therefore just beginning to be appreciated. Here we review some of the latest evidence showing that pools of PtdIns-3-P can be generated upon cellular stimulation in compartments different from the "classical" endosomal region. We describe several proteins that can be targets in mediating signals deriving from such stimulated PtdIns-3-P pools. In addition we describe the potential mechanism of switching on and off such signals. Taken together all this evidence suggest a novel, key role for PtdIns-3-P in signal transduction.