Phosphoinositide phosphatases in cell biology and disease.
Phosphoinositides are essential signaling molecules linked to a diverse array of cellular processes in eukaryotic cells. The metabolic interconversions of these phospholipids are subject to exquisite spatial and temporal regulation executed by arrays of phosphatidylinositol (PtdIns) and phosphoinositide-metabolizing enzymes. These include PtdIns- and phosphoinositide-kinases that drive phosphoinositide synthesis, and phospholipases and phosphatases that regulate phosphoinositide degradation. In the past decade, phosphoinositide phosphatases have emerged as topics of particular interest. This interest is driven by the recent appreciation that these enzymes represent primary mechanisms for phosphoinositide degradation, and because of their ever-increasing connections with human diseases. Herein, we review the biochemical properties of six major phosphoinositide phosphatases, the functional involvements of these enzymes in regulating phosphoinositide metabolism, the pathologies that arise from functional derangements of individual phosphatases, and recent ideas concerning the involvements of phosphoinositide phosphatases in membrane traffic control.
Liu
Yang
Y
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7090, USA.
Bankaitis
Vytas A
VA
D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D004194:Disease / Q000235:genetics; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C121116:TPIP (protein); C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C446603:TPTE protein, human; C099588:myotubularin; D000072181:Inositol Polyphosphate 5-Phosphatases; D051059:PTEN Phosphohydrolase