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Research Activities

Overview

   
     

Lipid Second Messengers and Phospholipases

Characterization of Phospholipase A2

Inhibitors and Cellular Studies

Membrane Phenomenon and Surface Dilution Kinetics

 

Other Novel Enzymes

Our research program has focused mainly on phospholipase A2 and macrophages as a prototype signal transduction system. We are also carrying out studies on phospholipase D (30) and lysophospholipases (31) and have cloned and characterized a novel mammalian lysophospholipase (32). We have also studied the regiospecificity of the important lysophospholipase activity of the Group IV cPLA2 (33). Additionally, we discovered a phosphatidate phosphohydrolase in macrophages (34) and a novel signaling molecule, diacylglycerol pyrophosphate (35), which it breaks down. We have also examined signal transduction in human amnionic cells with an aim to understand the role of PLA2 in parturition (36,37). Of special importance, we are currently identifying additional novel phospholipases and their role in signal transduction including those effecting sphingomyelin synthesis (38). One area of new work is to look at the role of PLA2s involved in Alzheimer’s disease and ischemia.
 

Oxidized Lipids

 
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Significant References
  1. Balboa, M.A., Balsinde, J., Dennis, E.A., and Insel, P.A., A Phospholipase D-Mediated Pathway for Generating Diacylglycerol in Nuclei from Madin-Darby Canine Kidney Cells, J.Biol.Chem., 270, 11738-11740 (1995).
  2. Wang, A., Deems, R.A., and Dennis, E.A., Cloning, Expression and Catalytic Mechanism of Murine Lysophospholipase I, J.Biol.Chem., 272, 12723-12729 (1997).
  3. Wang, A., Loo, R.W., Chen, Z., and Dennis, E.A., Regiospecificity and Catalytic Triad of Lysophospholipase I, J.Biol.Chem., 272, 22030-22036 (1997).
  4. Loo, R.W., Conde-Frieboes, K., Reynolds, L.J., and Dennis, E.A., Activation, Inhibition, and Regiospecificity of the Lysophospholipase Activity of the 85 kDa Cytosolic Group IV Phospholipase A2, J.Biol.Chem., 272, 19214-19219 (1997).
  5. Balsinde, J. and Dennis, E.A., Bromoenol Lactone Inhibits Magnesium-dependent Phosphatidate Phosphohydrolase and Blocks Triacylglycerol Biosynthesis in Mouse P388D1 Macrophages, J.Biol.Chem., 271, 31937-31941 (1996).
  6. Balboa,M.A., Balsinde,J., Dillon,D.A., Carman,G.M., and Dennis,E.A., Proinflammatory Macrophage-Activating Properties of the Novel Phospholipid Diacylglycerol Pyrophosphate, J.Biol.Chem., 274, 522-526 (1999).
  7. Balboa, M.A., Balsinde, J., and Dennis, E.A., Involvement of Phosphatidate Phosphohydrolase in Arachidonic Acid Mobilization in Human Amnionic WISH Cells, J.Biol.Chem., 273, 7684-7690 (1998).
  8. Johnson,C.A., Balboa,M.A., Balsinde,J., and Dennis,E.A., Regulation of Cyclooxygenase-2 Expression by Phosphatidate Phosphohydrolase in Human Amnionic WISH Cells, J.Biol.Chem., 274, 27689-27693 (1999).
  9. Balsinde, J., Balboa, M.A., and Dennis, E.A., Inflammatory Activation of Arachidonic Acid Signaling via Sphingomyelin Synthase, J.Biol.Chem., 272, 20373-20377 (1997).
Webmaster: Ursula Kessen, 2005