Phosphatidylinositol 5-phosphate (PtdIns5P), the most recently discovered phosphoinositide, has been proposed to play a role as a lipid mediator of intracellular Signaling. We have previously Shown that PtdIns5P generated by IpgD, all effector of the causative agent of dysentery Shigella flexneri, activates the PI 3-kinase/Akt pathway. Here, we demonstrate that PtdIns5P is able to protect Akt from dephosphorylation. This effect is not due to inhibition of the phosphoinositide phosphatase regulating,g PtdIns(3,4,5)P-3 levels PTEN but rather to PtdIns5P-induced phosphorylation and subsequent inhibition of the catalytic subunit of PP2A phosphatases. These data shed light oil a new mechanism used by S.fluxneri bacteria to sustain Akt activation to increase Survival Of the host Cells during bacterial replication. (C) 2009 Elsevier Inc. All rights reserved.