Signalling roles of mammalian phospholipase D1 and D2.
Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine to generate the lipid second messenger, phosphatidate (PA) and choline. PLD activity in mammalian cells is low and is transiently stimulated upon activation by G-protein-coupled and receptor tyrosine kinase cell surface receptors. Two mammalian PLD enzymes (PLD1 and PLD2) have been cloned and their intracellular regulators identified as ARF and Rho proteins, protein kinase Calpha as well as the lipid, phosphatidylinositol bisphosphate (PIP2). I discuss the regulation of these enzymes by cell surface receptors, their cellular localisation and the potential function of PA as a second messenger. Evidence is presented for a role of PA in regulating the lipid kinase activity of PIP 5-kinase, an enzyme that synthesises PIP2. A signalling role of phospholipase D via PA and indirectly via PIP2 in regulating membrane traffic and actin dynamics is indicated by the available data.
Cockcroft
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S
Department of Physiology, University College London, United Kingdom. ucgbsxc@ucl.ac.uk
D000818:Animals; D002460:Cell Line; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology; D008856:Microscopy, Fluorescence; D010712:Phosphatidic Acids / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015290:Second Messenger Systems / Q000502:physiology*; D015398:Signal Transduction
D007527:Isoenzymes; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D019269:Phosphatidylinositol 4,5-Diphosphate; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1