Phospholipases: Generation of Lipid-Derived Second Messengers

  • Mary F. Roberts
Part of the Hormones in Health and Disease book series (HHD)


Phospholipases are lipolytic enzymes that play key roles in signal transduction by generating both lipid and in some cases soluble second messengers. Their catalytic properties are often exquisitely controlled by phosphorylation, interaction with other proteins (e.g., GTP-binding proteins), as well as interaction with other lipids. Most of these proteins fall into the category of peripheral membrane proteins. An important aspect of these enzymes is that while they are in general water-soluble, the carry out their catalysis at an interface. This complicates kinetics because the dimensionality of the reaction has changed from a single phase (bulk solution) to two phases (the phospholipid aggregate interface as well as the bulk solution). Often there is a separate binding domain /site for the interface as well as for the active site. Such multiple functional sites can be modular or incorporated into a single area of the protein. A recurring theme is that there are mechanisms that enhance protein association with the inteface. This in turn increases the local concentration of substrate (and in some cases chemically modifies the protein) such that catalytic efficiency is increased. These secondary sites can serve to regulate enzyme activity by controlling access to substrate. However, there are often other modes of regulation that interwine phospholipases with other signal transduction proteins.


Bacillus Cereus Aristolochic Acid Fatty Acyl Chain Arachidonic Acid Release Cytosolic Phospholipase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Aboulsalham A, Liossis C, O’Brien L, and Brindley DN. 1997. Cell-permeable ceramides prevent the activation of phospholipase D by ADP-ribosylation factor and RhoA. J Biol Chem 272:1069–1075.Google Scholar
  2. Ackermann EJ, Kempner ES, and Dennis EA. 1994. Ca2+-independent cytosolic phospholipase A2 from macrophage-like P388D1 cells. Isolation and characterization. J Biol Chem 269:9227–9233.PubMedGoogle Scholar
  3. Allgyer TT and Wells MA. 1979. Phospholipase D from savoy cabbage: purification and preliminary kinetic characterization. Biochemistry 18:5348–5353.PubMedGoogle Scholar
  4. Artursson E and Puu G. 1992. A phosphatidylinositol-specific phospholipase C from Cytophaga: Production, purification, and properties. Can J Microbiol 38:334–1337.Google Scholar
  5. Balboa MA, Balsinde J, Jones SS, and Dennis EA. 1997. Identity between the Ca2+-independent phospholipase A2 enzymes from P388D1 macrophages and Chinese hamster ovary cells. J Biol Chem 272:8576–8580.PubMedGoogle Scholar
  6. Balsinde J, Balboa MA, Insel PA, and Dennis EA. 1997. Differential regulation of phospholipase D and phospholipase A2 by protein kinase C in P388D1 macrophages. Biochem J 321:805–809.PubMedGoogle Scholar
  7. Basanez G, Fidelio GD, Goni FM, Maggio B, and Alonso A. 1996a. Dual inhibitory effect of gangliosides on phospholipase C-promoted fusion of lipidic vesicles. Biochemistry 35:7506–7513.PubMedGoogle Scholar
  8. Basanez G, Nieva JL, Goni FM, and Alonso A. 1996b. Origin of the lag period in the phospholipase C cleavage of phospholipids in membranes. Concomitant vesicle aggregation and enzyme activation. Biochemistry 35:15183–15187.PubMedGoogle Scholar
  9. Bauldry SA and Wooten RE. 1997. Induction of cytosolic phospholipase A2 by phosphatidic acid and diglycerides in permeabilized human neutrophils: interrelationship between phospholipase D and A2. Biochem J 322:353–363.PubMedGoogle Scholar
  10. Bayburt T and Gelb MH. 1997. Interfacial catalysis by human 85 kDa cytosolic phospholipase A2 on anionic vesicles in the scooting mode. Biochemistry 36:3216–3231.PubMedGoogle Scholar
  11. Bennet CF, Balcarek JM, Varrichio A, and Crooke ST. 1988. Molecular cloning and complete amino acid sequence of form-1 phosphoinositide-specific phospholipase C. Nature 334:268–270.Google Scholar
  12. Bertagnolo V, Mazzoni M, Ricci D, Carini C, Neri LM, Previati M, and Capitani S. 1995. Identification of PI-PLC βl, γl, and δ1 in rat liver: subcellular distribution and relationship to inositol lipid nuclear signaling. Cell Signal 7:669–678.PubMedGoogle Scholar
  13. Bian J and Roberts ME 1992. Comparison of surface properties and thermody-namic behavior of lyso-and diacylphosphatidylcholines. J Coll Int Sci 153: 420–428.Google Scholar
  14. Billah MM and Anthes JC. 1990. The regulation and cellular functions of PC hydrolysis. Biochem J 269:281–291.PubMedGoogle Scholar
  15. Biltonen RL, Heimburg TR, Lathrop BK, and Bell JD. 1991. Molecular aspects of phospholipase A2 activation. In: Mukherjee AB, ed. Biochemistry, molecular biology, and physiology of phospholipase A2 and its regulatory factors. New York: Plenum Publishing Corp. 86–103.Google Scholar
  16. Birrell GB, Hedberg KK, and Griffith OH. 1995. An extracellular inositol phos-pholipid-specific phospholipase C is released by cultured Swiss 3T3 cells. Biochem Biophys Res Commun 211:318–324.PubMedGoogle Scholar
  17. Brindley DN, Abousalham A, Kikuchi Y, Wang CN, and Waggoner DW. 1996.66 Cross talk between the bioactive glycerolipids and sphingolipids in signal transduc-tion. Biochem Cell Biol 74:469–476.PubMedGoogle Scholar
  18. Brindley DN and Waggoner DW. 1996. Phosphatidate phosphohydrolase in signal transduction. Chem Phys Lipids 80:45–57.PubMedGoogle Scholar
  19. Brunie S, Bolin J, Gewirth D, and Sigler PB. 1985. The refined crystal structure of dimeric phospholipase A2 at 2.5Å. Access to a shielded catalytic center. J Biol Chem 260:9742–9749.PubMedGoogle Scholar
  20. Buergess WH, Dionne CA, Kaplow J, Mudd R, Friesel R, Zilberstein A, Schlessinger J, and Jaye M. 1990. Characterization and cDNA cloning of phospholipase C-γ, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. Mol Cell Biol 10:4770–4777.Google Scholar
  21. Camilli A, Goldfine H, and Portnoy DA. 1991. Listeria monocytogenes mutants lacking phosphatidylinositol-specific phospholipase C are avirulent. J Exp Med 173:751–754.PubMedGoogle Scholar
  22. Carman G, Deems RA, and Dennis EA. 1995. Lipid signaling enzymes and surface dilution kinetics. J Biol Chem 270:18711–18714.PubMedGoogle Scholar
  23. Carozzi A, Camps M, Gierschik P, and Parker P. 1993. Activation of phosphatidyli-nositol lipid-specific phospholipase C-β3 by G-protein β03B3 subunits. FEBS Lett 315:340–342.PubMedGoogle Scholar
  24. Clark JD, Lin L, Kriz RW, Ramesha CS, Sultzman LA, Lin AY, Milona N, and Knopf JL. 1991. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP. Cell 65:1043–1051.PubMedGoogle Scholar
  25. Clark MA Shorr RGL and Bomalski JS. 1986. Antibodies prepared to Bacillus cereus phospholipase C crossreact with a phosphatidylcholine preferring phospholipase C in mammalian cells. Biochem Biophys Res Commun 140:14–119.Google Scholar
  26. Cockcroft S. 1992. G-protein regulated phospholipases C, D, and A2-mediated signaling in permeabilized neutrophils. Biochim Biophys Acta 1113:135–160.PubMedGoogle Scholar
  27. Cockcroft S and Thomas GMH. 1992. Inositol-lipid-specific phospholipase C isoen-zymes and their differential regulation by receptors. Biochem J 288:1–14.PubMedGoogle Scholar
  28. Colley WC, Sung TC, Roll R, Jenco J, Hammond SM, Altshuller Y, Bar-Sagi D, Morris AJ, and Frohman MA. 1997. Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization. Curr Biol 7:191–201.PubMedGoogle Scholar
  29. Corssen J. 1996. Phospholipase activation and secretion: evidence that PLA2, PLC, and PLD are not essential to exocytosis. Am J Physiol 270:C1153–C1163.Google Scholar
  30. Daniele JJ, Maggio B, Bianco ID, Goni FM, Alonso A, and Fidelio GD. 1996. Inhibition by gangliosides of Bacillus cereus phospholipase C activity against monolayers, micelle, and bilayer vesicles. Eur J Biochem 239:105–110.PubMedGoogle Scholar
  31. Danin M, Chalifa V, Mohn H, Schmidt U-S, and Liscovitch M. 1993. Rat brain membrane-bound phospholipase D. In: Fain JN, ed. Lipid metabolism in signaling systems. New York: Academic Press. 14–24.Google Scholar
  32. Davitz MA, Hereld D, Shak S, Krakow J, Englund PT, and Nussenzweig V. 1987. A glycanphosphatidylinositol-specific phospholipase D in human serum. Science 238:81–84.PubMedGoogle Scholar
  33. DeHaas GH, Bonsen PPM, Pieterson WA, and Van Deenen LLM. 1971. Studies on phospholipase A2 and its zymogen from porcine pancreas. Biochim Biophys Acta 239:252–266.Google Scholar
  34. Dennis EA. 1997. The growing phospholipase A2 superfamily of signal transduction enzymes. Trends Biochem Sci 22:1–2.PubMedGoogle Scholar
  35. Dennis EA. 1973. Phospholipase A2 activity towards phosphatidylcholine in mixed micelles: surface dilution kinetics and the effects of thermotropic phase transitions. Arch Biochem Biophys 158:485–493.PubMedGoogle Scholar
  36. Dijkstra BW, Kalk KH, Hoi WGJ, and Drenth J. 1981. Structure of bovine pancreatic phospholipase A2 at 1.7 Å. J Mol Biol 147:97–123.PubMedGoogle Scholar
  37. Dijkstra BW, Renetseder R, Kalk KH, Hoi WGJ, and Drenth J. 1983. Structure of porcine pancreatic phospholipase A2 at 2.6Å resolution and comparison with bovine phospholipase A2. J Mol Biol 168:163–179.PubMedGoogle Scholar
  38. Dua R, Wu S-K, and Cho W. 1995. A structure-function study of bovine pancreatic phospholipase A2 using polymerized mixed liposomes. J Biol Chem 270:263–268.PubMedGoogle Scholar
  39. Ella KM, Dolan JW, and Meier KE. 1995. Characterization of a regulated form of phospholipase D in the yeast Saccharomyces cerevisiae. Biochem J 307:799–805.PubMedGoogle Scholar
  40. Ellis MV and Katan M. 1995. Mutations within a highly conserved sequence present in the X region of phosphoinositide-specific phospholipase C δ1. Biochem J 307:69–75.PubMedGoogle Scholar
  41. Emori Y, Homma Y, Sorimachi H, Kawasaki H, Nakanishi O, Suzuki K, and Tak-enawa T. 1989. A second type of rat phosphoinositide-specific phospholipase C containing a src-related sequence not essential for phosphoinositide hydrolyz-ing activity. J Biol Chem 264:21885–21890.PubMedGoogle Scholar
  42. English D. 1996. Phosphatidic acid: a lipid messenger involved in intracellular and extracellular signaling. Cell Signal 8:341–347.PubMedGoogle Scholar
  43. Essen L-O, Perisic O, Cheung R, Katan M, and Williams R. 1996. Crystal structure of a mammalian phosphoinositide-specific phospholipase Cδ. Nature 380:595–602.PubMedGoogle Scholar
  44. Essen L-O, Perisic O, Katan M, Wu Y, Roberts MF, and Williams R. 1997. Structural mapping of the catalytic mechanism for a mammalian phosphoinositide-specific phospholipase C. Biochemistry 36:1704–1718.PubMedGoogle Scholar
  45. Exton J. 1990. Signaling through PC breakdown. J Biol Chem 265:4.Google Scholar
  46. Exton JH. 1997. Phospholipase D: Enzymology, mechanisms of regulation, and function. Physiol Rev 77:303–320.PubMedGoogle Scholar
  47. Farooqui AA, Rapoport SI, and Horrocks LA. 1997. Membrane phospholipid alterations in Alzheimer’ disease: deficiency of ethanolamine plasmalogens. Neuro-chem Res 22:523–527.Google Scholar
  48. Farooqui AA, Yang HC, and Horrocks LA. 1995. Plasmalogens, phospholipases A2 and signal transduction. Brain Res Rev 21:152–161.PubMedGoogle Scholar
  49. Fensome A, Cunningham E, Prosser S, Tan SK, Swigart P, Thomas G, Hsuan J, and Cockcroft S. 1996. ARF and PITP restore GTPγS-stimulated protein secretion from cytosol-depleted HL60 cells by promoting PIP2 synthesis. Curr Biol 6:730–738.PubMedGoogle Scholar
  50. Ferguson MA Low MG and Cross GAM. 1985. Glycosyl-sn-l,2-dimyristoyl-phos-phatidylinositol is covalently linked to Trypanosoma brucei variant surface glycoprotein. J Biol Chem 260:14547–14555.PubMedGoogle Scholar
  51. Fisher A, Dodia C, and Chander A. 1994. Inhibition of lung calcium-independent phospholipase A2 by surfactant protein A. Am J Physiol 267:L335–L341.PubMedGoogle Scholar
  52. Fisher A, Dodia C, Chander A, and Jain M. 1992. A competitive inhibitor of phos-pholipase A2 decreases surfactant phosphatidylcholine degradation by the rat lung. Biochem J 288:407–411.PubMedGoogle Scholar
  53. Fisher AB and Dodia C. 1997. Role of acidic Ca2+-independent phospholipase A2 in synthesis of lung dipalmitoyl phosphatidyleholine. Am J Physiol 272:L238–L243.PubMedGoogle Scholar
  54. Friedman P, Markman O, Haimovitz R, Roberts MF, and Shinitzky M. 1995. Conversion of lysophospholipids to cyclic lysophosphatidic acid by phospholipase D. J Biol Chem 271:953–957.Google Scholar
  55. Garigapati V, Bian J, and Roberts MF. 1995. Synthesis and characterization of short-chain diacyl phosphatidic acids. J Coll & Int Sc. 169:486–492.Google Scholar
  56. Gelb MH, Jain MK, Hanel AM, and Berg OG. 1995. Interfacial enzymology of glycerolipid hydrolases: Lessons from secreted phospholipases A2. Annu Rev Biochem 64:653–688.PubMedGoogle Scholar
  57. Griffith OH, Volwerk JJ, and Kuppe A. 1991. Phosphatidylinositol-specific phospholipase C from Bacillus cereus and Bacillus thuringiensis. Methods Enzymol 197:493–502.PubMedGoogle Scholar
  58. Grobler JA and Hurley JH. 1996. Expression, characterization, and crystallization of the catalytic core of rat phosphatidylinositide-specific phospholipase C δ1. Protein Sci 5:680–686.PubMedGoogle Scholar
  59. Guillouard I, Gamier T, and Cole ST. 1996. Use of site-directed mutagenesis to probe structure-function relationships of α-toxin from Clostridium perfringens. Infect Immunol 64:2440–2444.Google Scholar
  60. Hack CE, Wolbink GJ, Schalkwijk C, Speijer H, Hermens WT, and van den Bosch H. 1997. A role for the secretory phospholipase A2 and C-reactive protein in the removal of injured cells. Immunol Today 18:111–115.PubMedGoogle Scholar
  61. Hammond SM, Altshuller YM, Sung TC, Rudge SA, Rose K, Engebrecht J, Morris AJ, and Frohman MA. 1995. Human ADP-ribosylation factor-activated phos-phatidylcholine-specific phospholipase D defines a new and highly conserved gene family. J Biol Chem 270:29640–29643.PubMedGoogle Scholar
  62. Han SK, Yoon ET, Scott DL, Sigler PB, and Cho W. 1997. Structural aspects of interfacial adsorption. A crystallographic and site-directed mutagenesis study of the phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus. J Biol Chem 272:3573–3582.PubMedGoogle Scholar
  63. Hansen S, Hansen LK, and Hough E. 1992. Crystal structures of phosphate, iodide, and iodate-inhibited phospholipase C from Bacillus cereus and structural investigations of the binding of reaction products and a substrate analogue. J Mol Biol 225:543–549.PubMedGoogle Scholar
  64. Hansen S, Hough E, Svensson LA, Wong Y-L, and Martin SF. 1993. Crystal structure of phospholipase C from Bacillus cereus complexed with a substrate analog. J Mol Biol 234:79–187.Google Scholar
  65. Harlan JE, Hajduk PJ, Yoon HS, and Fesik SW. 1994. Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate. Nature 371:168–170.PubMedGoogle Scholar
  66. Hattori K, Hattori M, Adachi H, Tsujimoto M, Artai H, and Inoue K. 1995. Purification and characterization of platelet-activating factor acetylhydrolase II from bovine liver cytosol. J Biol Chem 270:22308–22313.PubMedGoogle Scholar
  67. Hattori M, Adachi H, Tsujimoto M, Arai H, and Inoue K. 1994. The catalytic subunit of bovine brain platelet-activating factor acetylhydrolase is a novel type of serine esterase. J Biol Chem 269:23150–23155.PubMedGoogle Scholar
  68. Hattori M, Adachi H, Tsujimoto M, Arai H, and Inoue K. 1994. Miller-Dieker Iissencephaly gene encodes a subunit of brain platelet-activating factor. Nature 370:216–218.PubMedGoogle Scholar
  69. Hattori M, Arai H, and Inoue K. 1993. Purification and characterization of bovine brain platelet-activating factor acetylhydrolase. J Biol Chem 268: 8748–18753.Google Scholar
  70. Heinz DW, Ryan M, Bullock T, and Griffith OH. 1995. Crystal structure of the phosphatidylinositol-specific phospholipase C from Bacillus cereus in complex with myo-inositol. EMBO J 14:3855–3863.PubMedGoogle Scholar
  71. Heinz DW, Ryan M, Smith MP, Weaver LH, Keana JF, and Griffith OH. 1996. Crystal structure of phosphatidylinositol-specific phospholipase C from Bacillus cereus in complex with glucosaminyl(α1-6)-D-myo-inositol, an essential fragment of GPI anchors. Biochemistry 35:9496–9504.PubMedGoogle Scholar
  72. Heller M. 1978. Phospholipase D. Adv Lipid Res 16:267–326.PubMedGoogle Scholar
  73. Hendrickson HS, Banovetz C, Kirsch MJ, and Hendrickson EK. 1996. Kinetics of phosphatidylinositol-specific phospholipase C with vesicles of a thiophosphate analogue of phosphatidylinositol. Chem Phys Lipids 84:87–92.PubMedGoogle Scholar
  74. Higgs HN and Glomset J A. 1994. Identification of a phosphatidic acid-preferring phospholipase A1 from bovine brain and testis. Proc Natl Acad Sci USA 91:9574–9578.PubMedGoogle Scholar
  75. Homma Y, Emori Y, Shibasaki F, Suzuki K, and Takenawa T. 1990. Isolation and characterization of a γ-type phosphoinositide specific phospholipase C (PLC-γ2). Biochem J 269:13–18.PubMedGoogle Scholar
  76. Hou W, Arita Y, and Morisset J. 1996. Basic fibroblast growth factor-stimulated arachidonic acid release in rat pancreatic acini: sequential action of tyrosine kinase, phospholipase C, protein kinase C, and diacylglycerol lipase. Cell Signal 8:487–496.PubMedGoogle Scholar
  77. Hough E, Hansen LK, Birknes B, Jynge K, Hansen S, Hordvik A, Little C, Dodson E, and Derewenda Z. 1989. High-resolution (1.5Å) crystal structure of phospholipase C from Bacillus cereus. Nature 338:57–360.Google Scholar
  78. Huang PS, Davis L, Huber H, Goodhart PJ, Wegrzyn RE, Oliff A, and Heimbrook DC. 1995. An SH3 domain is required for the mitogenic activity of microin-jected phospholipase C-γ1. FEBS Lett 358:287–292.PubMedGoogle Scholar
  79. Ikezawa H and Taguchi T. 1981. Phosphatidylinositol-specific phospholipase C from Staphylococcus aureus. Methods Enzymol 71:731–741.Google Scholar
  80. Ishizaki J, Hanasaki K, Higashino K, Kishino J, Kibuchi N, Ohara O, and Arita H. 1994. Molecular cloning of pancreatic group I phospholipase A2 receptor. J Biol Chem 269:5897–5904.PubMedGoogle Scholar
  81. Jager K, Stieger S, Brodbeck U. 1991. Cholinesterase Solubilizing factor from cyto-phaga sp. is a phosphatidylinositol-specific phospholipase C. Biochim. Biophys. Acta, 1074:45–51PubMedGoogle Scholar
  82. Jain MK and Gelb MH. 1991. Phospholipase A2 catalyzed hydrolysis of vesicles: uses of interfacial catalysis in the scooting mode. Methods in Enzymol 197:112–125.Google Scholar
  83. Jiang Y, Lu Z, Zang Q, and Foster DA. 1996. Regulation of phosphatidic acid phosphohydrolase by epidermal growth factor. Reduced association with the EGF receptor followed by increased association with protein kinase C ε. J Biol Chem 271:29529–29532.PubMedGoogle Scholar
  84. Johansen T, Bjorkoy G, Overvatn A, Diaz-Meco MT, Traavik T, and Moscat J. 1994. NIH 3T3 cells stably transfected with the gene encoding phosphatidylcholine-hydrolyzing phospholipase C from Bacillus cereus acquire a transformed phe-notype. Mol Cell Biol 14:646–654.PubMedGoogle Scholar
  85. Johansen T, Holm T, Guddal PH, Sletten K, Haugli FB, and Little C. 1988. Cloning and sequencing of the gene encoding the phosphatidylcholine-preferring phospholipase C of Bacillus cereus. Gene 65:293–304.PubMedGoogle Scholar
  86. Kahn RA, Terui T, and Randazzo PA. 1996. Effects of acid phospholipids on ARF activities: potential roles in membrane traffic. J Lipid Mediat Cell Signal 14:209–214.PubMedGoogle Scholar
  87. Kanfer J. 1980. The base exchange enzymes and phospholipase D of mammalian tissue. Can J Biochem 58:1370–1380.PubMedGoogle Scholar
  88. Kim HK, Kim JW, Zilberstein A, Margolis B, Kim JG, Schlessinger J, and Rhee SG. 1991. PDGF Stimulation of inositol prospholipid hydrolysis requires PLC-gamma 1 phosphorylation on tyrosine residues 783 and 1254. Cell, 65:435–441.PubMedGoogle Scholar
  89. Kim JW, Ryu SH, and Rhee SG. 1989. Cyclic and noncyclic inositol phosphates are formed at different ratios by phospholipase C isozymes. Biochem Biophys Res Commun 163:177–182.PubMedGoogle Scholar
  90. Koblan KS, Schaber MD, Edwards G, Gibbs JB, and Pompliano DL. 1995. Src-ho-mology 2 (SH2) domain ligation as an allosteric regulator: Modulation of phos-phoinositide-specific phospholipase Cγ1 structure and activity. Biochem J 305:745–751.PubMedGoogle Scholar
  91. Kramer RM, Roberts EF, Manetta J, and Putnam JE. 1991. The Ca2+-sensitive cytosolic phospholipase A2 is a 100 kDA protein in human monoblast U937. J Biol Chem 266:5268–5272.PubMedGoogle Scholar
  92. Ktistakis NT, Brown HA, Waters MG, Sternweis PC, and Roth MG. 1996. Evidence that phospholipase D mediates ADP ribosylation factor-dependent formation of Golgi coated vesicles. J Cell Biol 134:295–306.PubMedGoogle Scholar
  93. Kudo I, Murakami M, Hara S, and Inoue K. 1993. Mammalian non-pancreatic phospholipase A2. Biochim Biophys Acta 1170:217–231.PubMedGoogle Scholar
  94. Kuhn B, Schmid A, Harteneck C, Gudermann T, and Schultz G. 1996. G-proteins of the Gq family couple the H2 histamine receptor to phospholipase C. Mol Endocrinol 10:1697–1707.PubMedGoogle Scholar
  95. Kundu GC and Mukherjee AB. 1997. Evidence that porcine pancreatic phospholipase A2 via its high affinity receptor stimulates extracellular matrix invasion by normal and cancer cells. J Biol Chem 272:2346–2353.PubMedGoogle Scholar
  96. Lambeau G, Ancian P, Barhanin J, and Lazdunski M. 1994. Cloning and expression of a membrane receptor for secretory phospholipases A2. J Biol Chem 269:1757–1578.Google Scholar
  97. Lee KY, Ryu SH, Suh PG, Choi WC, and Rhee SG. 1987. Phospholipase C associated with particulate fractions of bovine brain. Proc Natl Acad Sci USA 84:5540–5544.PubMedGoogle Scholar
  98. Lee YH, Lee HJ, Lee S-J, Min DS, Baek SH, Kim YS, Ryu SH, and Suh P-G. 1995. Down-regulation of phospholipase C-γ1 during the differentiation of U937 cells. FEBS Lett 358:105–108.PubMedGoogle Scholar
  99. Leimeister-Wachter M, Domann E, and Chakraborty T. 1991. Detection of a gene encoding a phosphatidylinositol-specific phospholipase C that is coordinately expressed with listeriolysin in Listeria monocytogenes. Mol Microbiol 5:361–366.PubMedGoogle Scholar
  100. Lereclus D, Agaisse H, Gominet M, Salamitou S, and Sanchis V. 1996. Identification of a Bacillus thuringiensis gene that positively regulates transcription of the phosphatidylinositol-specific phospholipase C gene at the onset of the stationary phase. J Bacteriol 178:2749–2756.PubMedGoogle Scholar
  101. Levine L, Xiao DM, and Little C. 1988. Increased arachidonic acid metabolites from cells in culture after treatment with the phosphatidylcholine-hydrolyzing phospholipase C from Bacillus cereus. Prostaglandins 34:633–642.Google Scholar
  102. Lewis K, Garigapati V, Zhou C, and Roberts MF 1993. Substrate requirements of bacterial phosphatidylinositol-specific phospholipase C. Biochemistry 32:8836–8841.PubMedGoogle Scholar
  103. Lin G, Bennett CF, and Tsai MD. 1990. Phospholipids chiral at phosphorus. Stereo-chemical mechanism of reactions catalyzed by phosphatidylinositide-specific phospholipase C from Bacillus cereus and guinea pig uterus. Biochemistry 29:2747–2757.PubMedGoogle Scholar
  104. Lin T-L, Chen S-H, and Roberts ME 1987. Thermodynamic analyses of the growth and structure of asymmetric linear short-chain lecithin micelles based on small angle neutron scattering data. J Amer Chem Soc 109:2321–2328.Google Scholar
  105. Little C. 1981. Effect of some divalent metal cations on phospholipase C from Bacillus cereus. Acta Chem Scand B35:39–44.Google Scholar
  106. Liu Y and Levy R. 1997. Phospholipase A2 has a role in proliferation but not in differentiation of HL-60 cells. Biochim Biophys Acta 1335:270–280.Google Scholar
  107. Low MG. 1981. Phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis. Methods Enzymol 71:741–746.PubMedGoogle Scholar
  108. Low MG and Huang K-S. 1993. Phosphatidic acid, lysophosphatidic acid and lipid A are inhibitors of glycosylphosphatidylinositol-specific phospholipase D: Specific inhibition of a phospholipase by product analogues? J Biol Chem 268:8480–8490.PubMedGoogle Scholar
  109. Low MG and Huang KS. 1991. Factors affecting the ability of glycosylphosphatidyli-nositol-specific phospholipase D to degrade the membrane anchors of cell surfaces. Biochem J 279:483–493.PubMedGoogle Scholar
  110. Lucas M, Sanchez-Margalet V, Pedrera C, and Bellido ML. 1995. A chemilumines-cence method to analyze phosphatidylcholine-phospholipase activity in plasma membrane preparations and in intact cells. Anal Biochem 231:277–281.PubMedGoogle Scholar
  111. Lukowski S, Lecomte MC, Mira JP, Marin P, Gautero H, Russo-Marie F, and Geny B. 1996. Inhibition of phospholipase D activity by fodrin. An active role for the cytoskeleton. J Biol Chem 271:24164–24171.PubMedGoogle Scholar
  112. Ma Z, Ramanadham S, Kempe K, Chi XS, Ladenson J, and Turk X 1997. Pancreatic islets express a Ca2+-independent phospholipase A2 that contains a repeated structural motif homologous to the integral membrane protein binding domain of ankyrin. J Biol Chem 272:11118–11127.PubMedGoogle Scholar
  113. Margolis B, Rhee SG, Felder S, Mervic M, Lyall R, Levitzki A, Ullrich A, Zilberstein A, and Schlessinger J. 1989. EGF induces tyrosine phosphorylation of phospholipase C-II: A potential mechanism for EGF receptor signaling. Cell 57:1101–1107.PubMedGoogle Scholar
  114. Martin SF, Spalier MR, and Hegenrother PJ. 1996. Expression and site-directed mutagenesis of the phosphatidylcholine-preferring phospholipase C of Bacillus cereus: probing the role of the active site Glu146. Biochemistry 35: 12970–12977.PubMedGoogle Scholar
  115. McDonald LJ and Mamrack MD. 1995. Phosphoinositide hydrolysis by phospholipase C modulated by multivalent cations La3+, Al3+, neomycin, poly amines, and melittin. J Lipid Mediat Cell Signal 11:81–91.PubMedGoogle Scholar
  116. McNamara PJ, Cuevas WA, and Songer JG. 1995. Toxic phospholipases D of Coryne-bacterium pseudotuberculosis, C. ulcerans and Arcanobacterium haemolyticum: cloning and sequence homology. Gene 156:113–118.PubMedGoogle Scholar
  117. Mengaud J, Braun-Breton C, and Cossart P. 1991. Identification of phosphatidyli-nositol-specific phospholipase C activity in Listeria monocyto genes: A novel type of virulence factor? Mol Microbiol 5:367–372.PubMedGoogle Scholar
  118. Mensa-Wilmot K and Englund PT. 1992. Glycosyl phosphatidylinositol-specific phospholipase C of Trypanosoma brucei: expression in Escherichia coli. Mol Biochem Parasitol 56:311–322.PubMedGoogle Scholar
  119. Morris JC, Lei P-S, Shen TY, and Kojo MW. 1995. Glycan requirements of glycosyl-phosphatidylinositol phospholipase C from Trypanosoma brucei. J Biol Chem 270:2517–2524.PubMedGoogle Scholar
  120. Morris JC, Ping-Sheng L, Zhai HX, Shen TY, and Mensa-Wilmot K. 1996. Phospha-tidylinositol phospholipase C is activated allosterically by the aminoglycoside G418. 2-deoxy-2-fluoro-scyllo-inositol-l-0-dodecylphosphonate and its analogs inhibit glycosylphosphatidylinositol phospholipase C. J Biol Chem 271:15468–15477.PubMedGoogle Scholar
  121. Nakamura S. 1996. Phosphatidylcholine hydrolysis and protein kinase C activation for intracellular signaling network. J Lipid Mediat Cell Signal 14:197–202.PubMedGoogle Scholar
  122. Nieva JL, Goni FM, and Alonso A. 1993. Phospholipase C-promoted membrane fusion: Retroinhibition by the end product diacylglycerol. Biochemistry 32:1054–1058.PubMedGoogle Scholar
  123. Nishizuka Y. 1992. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258:607–614.PubMedGoogle Scholar
  124. Offermanns S and Simon ML 1995. Gα15 and Gα16 couple a wide variety of receptors to phospholipase C. J Biol Chem 270:15175–15180.PubMedGoogle Scholar
  125. Olson SC and Lambeth JD. 1996. Biochemistry and cell biology of phospholipase D in human neutrophils. Chem Phys Lipids 80:3–19.PubMedGoogle Scholar
  126. Pascher I, Lundmark M, Nyholm P-G, and Sundell S. 1992. Crystal structures of phospholipids. Biochim Biophys Acta 1113:339–373.PubMedGoogle Scholar
  127. Pelech SL and Vance DE. 1989. Signal transduction via phosphatidylcholine cycles. Trends Biochem Sci 14:28–30.Google Scholar
  128. Pertile P, Liscovitch M, Chalifa V, and Cantley LC. 1995. Phosphatidylinositol 4,5-bisphosphate synthesis is required for activation of phospholipase D in U937 cells. J Biol Chem 270:5130–5135.PubMedGoogle Scholar
  129. Ponting CP and Kerr ID. 1996. A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues. Protein Sci 5:914–922.PubMedGoogle Scholar
  130. Qiu Z-H, de Carvalho MS, and Leslie CC. 1993. Regulation of phospholipase A2 activation by phosphorylation in mouse peritoneal macrophages. J Biol Chem 268:24506–24513.PubMedGoogle Scholar
  131. Renetseder R, Dijkstra BW, Huizing K, Kalk KH, and Drenth J. 1988. Crystal structure of bovine pancreatic phospholipase A2 covalently inhibited by p-bro-mophenacylbromide. J Mol Biol 200:181–188.PubMedGoogle Scholar
  132. Reynolds LJ, Hughes LL, Louis AI, Kramer RM, and Dennis EA. 1993. Metal ion and salt effects on the phospholipase A2. lysophospholipase, and transacylase activities of human cytosolic phospholipase A2. Biochim Biophys Acta 1167:272–280.PubMedGoogle Scholar
  133. Rhee SG and Choi KD. 1992. Regulation of inositol phospholipid-specific phospholipase C isozymes. J Biol Chem 267:12393–12396.PubMedGoogle Scholar
  134. Rhee SG, Suh PG, Ryu S-H, and Lee KY. 1989. Studies of inositol phospholipid-specific phospholipase C. Science 244:546–550.PubMedGoogle Scholar
  135. Roberts MF. 1991a. Using NMR spectroscopy to assay phospholipases. Methods Enzymol 197:31–48.PubMedGoogle Scholar
  136. Roberts MF. 1991b. Using short-chain phospholipids to assay phospholipases. Methods Enzymol 197:95–112.PubMedGoogle Scholar
  137. Roberts MF. 1996. Phospholipases: structural and functional motifs for working at an interface. FASEB J 10:1159–1172.PubMedGoogle Scholar
  138. Ryan M, Smith MP, Vinod TK, Lau WL, Keana JF, and Griffith OH. 1996. Synthesis, structure-activity relationships, and the effect of polyethylene glycol on inhibitors of phosphatidylinositol-specific phospholipase C from Bacillus cereus. J Med Chem 39:4366–4376.PubMedGoogle Scholar
  139. Sands WA, Clark JS, and Liew FY. 1994. The role of a phosphatidylcholine-specific phospholipase C in the production of diacylglycerol for nitric oxide synthesis in macrophages activated by IFN-γ and LPS. Biochem Biophys Res Commun 199:461–466.PubMedGoogle Scholar
  140. Sato T, Aoki J, Nagai Y, Dohmae N, Takio K, Doi T, and Inoue K. 1997. Serine phospholipid-specific phospholipase A that is secreted from activated platelets. A new member of the lipase family. J Biol Chem 272:2192–2198.PubMedGoogle Scholar
  141. Schlessinger J. 1994. SH2/SH3 signaling proteins. Curr Opin Genet Dev 4:25–30.PubMedGoogle Scholar
  142. Scott DL, White SP, Otwinowski Z, Yuan W, Gelb MH, and Sigler PB. 1990. Inter-facial catalysis: The mechanism of phospholipase A2. Science 250:1541–1546.PubMedGoogle Scholar
  143. Scott DL and Sigler PB. 1995. Structure and catalytic mechanism of secretory phospholipase A2. Adv Protein Chem 45:53–88.Google Scholar
  144. Scott DL, White SP, Browning JL, Rosa JJ, Gelb MH, and Sigler PB. 1991. Structures of free and inhibited human secretory phospholipase. A2 from inflammatory exudate. Science 254:1007–1010.PubMedGoogle Scholar
  145. Sharp JD, Pickard RT, Chiou XG, Manetta JV, Kovacevic S, Miller JR, Varshavsky AD, Roberts EF, Strifler BA, Brems DN, and Kramer RM. 1994. Serine 228 is essential for catalytic activities of 85-kDa cytosolic phospholipase A2. J Biol Chem 269:23250–23254.PubMedGoogle Scholar
  146. Sheffield MJ, Baker BL, Owen NL, Baker ML, and Bell JD. 1995. Enhancement of Agkistrodon piscivorus piscivorus venom phospholipase A2 activity toward phosphatidylcholine vesicles by lysolecithin and palmitic acid: Studies with fluorescent probes of membrane structure. Biochemistry 34:7796–7806.PubMedGoogle Scholar
  147. Siddiqi AR, Smith JL, Ross AH, Qiu RG, Symons M, and Exton JH. 1995. Regulation of phospholipase D in HL60 cells. Evidence for a cytosolic phospholipase D. J Biol Chem 270:8466–8473.PubMedGoogle Scholar
  148. Simon MI, Strathman MP, and Gautam N. 1991. Diversity of G-proteins in signal transduction. Science 252:802–808.PubMedGoogle Scholar
  149. Smith MR, Ryu S-H, Suh PG, Rhee SG, and Kung H-F. 1989. S-phase induction and transformation of quiescent NIH 3T3 cells by microinjection of phospholipase C. Proc Natl Acad Sci USA 86:3659–3663.PubMedGoogle Scholar
  150. Smrcka AV, Hepler JR, Brown KO, and Sternweis PO. 1991. Regulation of polyphos-phoinositide-specific phospholipase C activity by purified Gq. Science 250:804–807.Google Scholar
  151. Snitko Y, Yoon ET, and Cho W. 1997. High specificity of human secretory class II phospholipase A2 for phosphatidic acid. Biochem J 321:737–741.PubMedGoogle Scholar
  152. Soltys CE and Roberts MF. 1994. Fluorescence studies of phosphatidylcholine micelle mixing: Relevance to phospholipase kinetics. Biochemistry 33:11608–11617.PubMedGoogle Scholar
  153. Soltys CE, Bian J, and Roberts MF. 1993. Polymerizable phosphatidylcholines: Importance of phospholipid motions for optimum phospholipase A2 and C activity. Biochemistry 32:9545–9552.PubMedGoogle Scholar
  154. Spiegel S and Milstien S. 1996. Sphingoid bases and phospholipase D activation. Chem Phys Lipids 80:27–36.PubMedGoogle Scholar
  155. Spiegel S, Foster D, and Kolesnick R. 1996. Signal transduction through lipid second messengers. Curr Opin Cell Biol 8:159–167.PubMedGoogle Scholar
  156. Srivastava SP, Chen NQ, Liu YX, and Holtzman JL. 1991. Purification and characterization of a new isozyme of thiol:protein-disulfide oxidoreductase from rat hepatic microsomes. J Biol Chem 266:20337–20344.PubMedGoogle Scholar
  157. Street IP, Lin H-K, Laliberte F, Ghomashchi F, Wang Z, Perrier H, Tremblay NM, Huang Z, Weech PK, and Gelb MH. 1993. Slow-and tight-binding inhibitors of the 85-kDa human phospholipase A2. Biochemistry 32:5935–5940.PubMedGoogle Scholar
  158. Sundell S, Hansen S, and Hough E. 1994. A proposal for the catalytic mechanism in phospholipase C based on interaction energy and distance geometry calculations. Prot Engineer 7:571–577.Google Scholar
  159. Sutton RB, Davtetov BA, Berhuis AM, Sudhof TC, and Sprang SR. 1995. Structure of the first C-2 domain of synaptotagmin. A novel Ca2+/phospholipid binding mode. Cell 80:929–938.PubMedGoogle Scholar
  160. Swairjo M, Seaton BA, and Roberts MF. 1994. Effect of vesicle composition and curvature on the dissociation of phosphatidic acid in small unilamellar vesicles-a31P NMR study. Biochim Biophys Acta 1191:354–361.PubMedGoogle Scholar
  161. Taguchi R and Ikezawa H. 1978. Phosphatidylinositol-specific phospholipase C from Clostridium novyi type A. Arch Biochem Biophys 186:196–201.PubMedGoogle Scholar
  162. Tan T, Hehir MJ, and Roberts MF. 1997. Cloning, overexpression, refolding, and purification of the non-specific phospholipase C from Bacillus cereus. Prot Expr & Purif 10:365–372.Google Scholar
  163. Tan T and Roberts MF. 1996. Vanadate is a potent competitive inhibitor of phospholipase C from Bacillus cereus. Biochim Biophys Acta 1298:58–68.PubMedGoogle Scholar
  164. Tang J, Kriz R, Wolfman N, Shaffer M, Seehra J, and Jones SS. 1997. A novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs. J Biol Chem 272:8567–8575.PubMedGoogle Scholar
  165. Taylor SJ, Chae HZ, Rhee SG, and Exton JH. 1991. Activation of the βl isozyme of phospholipase C by a subunits of the Gq class of G-proteins. Nature 350:516–518.PubMedGoogle Scholar
  166. Thunnissen MMGM, Ab E, Kalk KH, Drenth J, Dijkstra BW, Kuipers OP, Dijkman R, de Haas GH, and Verheij HM. 1990. X-ray structure of phospholipase A2 complexed with a substrate derived inhibitor. Nature 347:689–691.PubMedGoogle Scholar
  167. Van den Berg B, Tessari M, Boelens R, Dijkman R, Kaptein R, de Haas GH, and Verheij HM. 1995a. Solution structure of porcine pancreatic phospholipase A2 complexed with micelles and a competitive inhibitor. J Biomol NMR 5:110–121.PubMedGoogle Scholar
  168. Van den Berg B, Tessari M, de Haas GH, Verheij HM, Boelens R, and Kaptein R. 1995b. Solution structure of porcine pancreatic phospholipase A2. EMBO J 14:4123–4131.PubMedGoogle Scholar
  169. van Dijk MCM, Muriana FJG, de Widt J, Hilkmann H, and van Blitterswijk WJ. 1997. Involvement of phosphatidylcholine-specific phospholipase C in platelet-derived growth factor-induced activation of the mitogen-activated protein kinase pathway in rat-1 fibroblasts. J Biol Chem 272:11011–11016.PubMedGoogle Scholar
  170. Vega QC, Cochet C, Filhol O, Chang CP, Rhee SG, and Gill GN. 1992. A site of tyrosine phosphorylation in the C terminus of the epidermal growth factor receptor is required to activate phospholipase C. Mol Cell Biol 12:128–135.PubMedGoogle Scholar
  171. Venable ME, Bielawska A, and Obeid LM. 1996. Ceramide inhibits phospholipase D in a cell-free system. J Biol Chem 271:24800–24805.PubMedGoogle Scholar
  172. Verheij HM, Slotboom AJ, and De Haas GH. 1981. Phospholipase A2: a model for membrane-bound enzymes. Rev Physiol Pharmacol 91:91–203.Google Scholar
  173. Vinggaard AM, Jensen T, Morgan CP, Cockcroft S, and Hansen HS. 1996. Didecanoyl phospatidylcholine is a superior substrate for assaying mammalian phospholi-pase D. Biochem J 319:861–864.PubMedGoogle Scholar
  174. Volwerk JJ, Shashidhar MS, and Kuppe A. 1990. Pi-specific PLC from Bacillus cereus combines intrinsic phosphotransferase and cyclic phosphodiesterase activities: a 31P NMR study. Biochemistry 29:8056–8062.PubMedGoogle Scholar
  175. Waggoner DW, Martin A, Dewald J, Gomez-Munoz A, and Brindley DN. 1995. Purification and characterization of a novel plasma membrane phosphatidate phosphohydrolase from rat liver. J Biol Chem 270:19422–19429.PubMedGoogle Scholar
  176. Wahl MI, Jones GA, Nishibe S, Rhee SG, and Carpenter G. 1992. Growth factor stimulation of phospholipase C-γ1 activity. J Biol Chem 267:10447–10456.PubMedGoogle Scholar
  177. Wang X. 1993. Phospholipases. In: Moore TS, ed. Lipid metabolism in plants. Boca Raton: CRC Press. 505–512.Google Scholar
  178. Wery J-P, Schevitz RW, Clawson D, Bobbitt JL, Dow ER, Gamboa G, Goodson T, Hermann RB, Kramer RM, McClure DB, Mihelich ED, Putnam JE, Sharp J, Stark DH, Teater C, Warrick MW, and Jones ND. 1991. Structure of recombinant human rheumatoid arthritic synovial fluid phospholipase A2 at 2.2 Å resolution. Nature 352:79–82.PubMedGoogle Scholar
  179. White SP, Scott DL, Otwinowski Z, Gelb MH, and Sigler PB. 1990. Crystal structure of cobra-venom phospholipase A2 in a complex with a transition-state analogue. Science 250:1560–1563.PubMedGoogle Scholar
  180. Wolf M and Gross RW. 1996. Expression, purification, and kinetic characterization of a recombinant 80-kDa intracellular calcium-dependent phospholipase A2. J Biol Chem 271:30879–30885.PubMedGoogle Scholar
  181. Wu L, Niemeyer B, Colly N, Socolich M, and Zuker CS. 1995. Regulation of PLC-mediated signaling in vivo by CDP-diacylglycerol synthase. Nature 373:216–222.PubMedGoogle Scholar
  182. Wu WI, Lin YP, Wang E, Merrill AHJ, and Carman GM. 1993. Regulation of phosphatidate phosphatase activity from the yeast saccharomyces cerevisiae by sphingoid bases. J Biol Chem 268:13830–13837.PubMedGoogle Scholar
  183. Wu Y, Williams RL, Katan M, and Roberts MF. 1997a. Phosphatidylinositol-specific phospholipase C δ1 activity towards micellar substrates, inositol 1,2-cyclic phosphate and other water soluble substrates: A sequential mechanism and allos-teric activation. Biochemistry 36:11223–11233.PubMedGoogle Scholar
  184. Wu Y, Zhou C, and Roberts ME 1997b. Stereocontrolled syntheses of water soluble inhibitors of phosphatidylinositol-specific phospholipase C: Inhibition enhanced by an interface. Biochemistry 36:356–363.Google Scholar
  185. Yu BZ, Ghomashchi F, Cajal Y, Armand RR, Berg OG, Gelb MH, and Jain MK. 1997. Use of an imperfect neutral diluent and outer vesicle layer scooting mode hydrolysis to analyze the interfacial kinetics, inhibition, and substrate preferences of bee venom phospholipase A2. Biochemistry 36:3870–3881.PubMedGoogle Scholar
  186. Zhou C and Roberts MF. 1997. Diacylglycerol partitioning and mixing in detergent micelles: Relevance to enzyme kinetics. Biochim Biophys Acta 1348:273–286.PubMedGoogle Scholar
  187. Zhou C, Qian X, and Roberts MF. 1997a. Allosteric activation of phosphatidylinosi-tol-specific phospholipase C: Phospholipid binding anchors the enzyme to the interface. Biochemistry 36:10089–10097.PubMedGoogle Scholar
  188. Zhou C, Wu Y, and Roberts ME 1997b. Activation of phosphatidylinositol-specific phospholipase C towards inositol l,2-(cyclic)-phosphate. Biochemistry 36:347–355.PubMedGoogle Scholar

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© Springer Science+Business Media New York 1999

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  • Mary F. Roberts

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