Phosphoinositides (PPIns) are lipid signaling molecules that act as master regulators of cellular signaling. Recent studies have revealed novel roles of PPIns in myriad cellular processes and multiple human diseases mediated by misregulation of PPIn signaling. This review will present a timely summary of recent discoveries in PPIn biology, specifically their role in regulating unexpected signaling pathways, modification of signaling outcomes downstream of integral membrane proteins, and novel roles in lipid transport. This has revealed new roles of PPIns in regulating membrane trafficking, immunity, cell polarity, and response to extracellular signals. A specific focus will be on novel opportunities to target PPIn metabolism for treatment of human diseases, including cancer, pathogen infection, developmental disorders, and immune disorders.
Keywords: Flippases; GPCR; Ion channels; Lipid kinases; Lipid signaling; Lipid transfer proteins; Membrane contact sites; Membrane trafficking; PI3P; PI4KB; PI4P; PIK3CA; PIP2; PIP3; Phosphatidylinositol; Phosphoinositide kinases; Phosphoinositides.
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