Emerging roles of phosphatidylinositol 3-monophosphate as a dynamic lipid second messenger.
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.
Falasca
Marco
M
Centre for Cardiovascular Biology and Medicine, Division of Medicine, University College London, 5 University Street, London, WC1E 6JJ, UK. m.falasca@ucl.ac.uk
Maffucci
Tania
T
D002465:Cell Movement / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D004075:Diglycerides; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D017346:Protein Serine-Threonine Kinases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D014157:Transcription Factors; C011439:1,2-diacylglycerol; C460141:FYCO1 protein, human; C435927:PLEKHA1 protein, human; C055525:phosphatidylinositol 3-phosphate; C508327:PXK protein, human; C099588:myotubularin