Role of Lipins in Regulating Phospholipase D Signalling

  • Author / Creator
    Capatos, Dora
  • A potential therapeutic target in cancer is phospholipase D (PLD), which converts phosphatidylcholine into phosphatidic acid, a lipid second messenger in cell signalling. The lipid phosphate phosphatases are considered to convert PLD-generated phosphatidic acid to diacylglycerol. However, the lipid phosphate phosphatases are integral membrane proteins with catalytic sites on the extracellular or lumenal sides of membranes whereas phosphatidic acid accumulates on the cytosolic leaflet of membranes. The other enzymes that dephosphorylate phosphatidic acid, the lipins, are cytosolic proteins that translocate to membranes. This project investigated whether lipin-1 and lipin-2 regulate PLD signalling. The results show that phosphatidic acid accumulation in breast cancer cells resulted from PLD1 and PLD2 activation and activity of calcium-dependent diacylglycerol kinases. Depletion of lipin-1 did not affect PLD-dependent phosphatidic acid accumulation in fibroblasts. This work provides the first evidence that increased phosphatidic acid phosphatase activity of lipins is associated with membranes in response to PLD stimulation.

  • Subjects / Keywords
  • Graduation date
    Spring 2013
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Holmes, Charles (Biochemistry)
    • Lehner, Richard (Cell Biology)
    • Brindley, David (Biochemistry)