Several routes for PtdIns5P metabolization have been proposed, suggesting the existence of distinct intracellular PtdIns5P pools. We have shown, in the case of bacterial infection by Shigella flexneri, that PtdIns5P production at the
Ritonavir membrane leads to PI 3-kinase/Akt activation [10]. The virulence factor IpgD, injected by the bacteria in the host cell, is a phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) 4-phosphatase [11] and generates PtdIns5P at the bacteria entry sites. Other studies suggest a role for PtdIns5P in the nucleus, where it can bind the PHD domain of the tumor suppressor inhibitor of growth protein-2 (ING2) and regulate p53 acetylation and apoptosis [12]. Another pool of PtdIns5P is likely to exist at intracellular membranes due to phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2) hydrolysis via the myotubularin family members of 3-phosphatases [13]. PtdIns5P levels can also be modulated by the type II PIP 4-kinase and the type I 4-phosphatase, which convert PtdIns5P into PtdIns(4,5)P2 and PtdIns(4,5)P2 into PtdIns5P, respectively, under UV or genotoxic stress conditions [14] and [15]. Finally, the 5-kinase PIKfyve has been proposed to be involved in PtdIns5P synthesis either directly via PtdIns
phosphorylation or indirectly via the production of PtdIns(3,5)P2 that could be in turn dephosphorylated by 3-phosphatases like myotubularins [16] and [17].
