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Phospholipase A2

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Encyclopedia of Signaling Molecules
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Synonyms

Arachidonic acid; cPLA2; iPLA2; Leukotriene; Phospholipid; Prostaglandin; sPLA2

Historical Background

Phospholipase A2 (PLA2) hydrolyzes the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. In the view of signal transduction, the PLA2 reaction has been considered to be of particular importance since arachidonic acid, one of the polyunsaturated fatty acids released by PLA2, is metabolized by cyclooxygenases and lipoxygenases to the potent lipid mediators prostaglandins and leukotrienes, which are often referred to as eicosanoids. In addition, lysophospholipids or their metabolites, such as lysophosphatidic acid (LPA) and platelet-activating factor (PAF), represent another class of lipid mediators. These lipid mediators exert numerous biological actions through their cognate G protein-coupled receptors on target cells. PLA2 has also been implicated in membrane glycerophospholipid remodeling, thereby contributing to cellular homeostasis.

The PLA2...

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References

  • Balestrieri B, Maekawa A, Xing W, Gelb MH, Katz HR, Arm JP. Group V secretory phospholipase A2 modulates phagosome maturation and regulates the innate immune response against Candida albicans. J Immunol. 2009;182:4891–8.

    Article  PubMed  CAS  Google Scholar 

  • Bao S, Song H, Wohltmann M, Ramanadham S, Jin W, Bohrer A, et al. Insulin secretory responses and phospholipid composition of pancreatic islets from mice that do not express Group VIA phospholipase A2 and effects of metabolic stress on glucose homeostasis. J Biol Chem. 2006;281:20958–73.

    Article  PubMed  CAS  Google Scholar 

  • Boilard E, Lai Y, Larabee K, Balestrieri B, Ghomashchi F, Fujioka D, et al. A novel anti-inflammatory role for secretory phospholipase A2 in immune complex-mediated arthritis. EMBO Mol Med. 2010;2:172–87.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bolotina VM. Orai, STIM1 and iPLA2β: a view from a different perspective. J Physiol. 2008;586:3035–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bonventre JV, Huang Z, Taheri MR, O’Leary E, Li E, Moskowitz MA, Sapirstein A. Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2. Nature. 1997;390:622–5.

    Article  PubMed  CAS  Google Scholar 

  • Boudreau LH, Duchez AC, Cloutier N, Soulet D, Martin N, Bollinger J, et al. Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation. Blood. 2014;124:2173–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Clark JD, Lin LL, Kriz RW, Ramesha CS, Sultzman LA, Lin AY, et al. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP. Cell. 1991;65:1043–51.

    Article  CAS  PubMed  Google Scholar 

  • Dessen A, Tang J, Schmidt H, Stahl M, Clark JD, Seehra J, et al. Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism. Cell. 1999;97:349–60.

    Article  PubMed  CAS  Google Scholar 

  • Escoffier J, Jemel I, Tanemoto A, Taketomi Y, Payre C, Coatrieux C, et al. Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice. J Clin Invest. 2010;120:1415–28.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fujioka D, Saito Y, Kobayashi T, Yano T, Tezuka H, Ishimoto Y, et al. Reduction in myocardial ischemia/reperfusion injury in group X secretory phospholipase A2-deficient mice. Circulation. 2008;117:2977–85.

    Article  CAS  PubMed  Google Scholar 

  • Guan M, Qu L, Tan W, Chen L, Wong CW. Hepatocyte nuclear factor-4 α regulates liver triglyceride metabolism in part through secreted phospholipase A2 GXIIB. Hepatology. 2011;53:458–66.

    Article  CAS  PubMed  Google Scholar 

  • Henderson WR, Chi EY, Bollinger JG, Tien YT, Ye X, Castelli L, et al. Importance of group X-secreted phospholipase A2 in allergen-induced airway inflammation and remodeling in a mouse asthma model. J Exp Med. 2007;204:865–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hoeft B, Linseisen J, Beckmann L, Müller-Decker K, Canzian F, Hüsing A, et al. Polymorphisms in fatty-acid-metabolism-related genes are associated with colorectal cancer risk. Carcinogenesis. 2010;31:466–72.

    Article  PubMed  CAS  Google Scholar 

  • Labonté ED, Pfluger PT, Cash JG, Kuhel DG, Roja JC, Magness DP, et al. Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity. FASEB J. 2010;24:2516–24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lambeau G, Gelb MH. Biochemistry and physiology of mammalian secreted phospholipases A2. Annu Rev Biochem. 2008;77:495–520.

    Article  CAS  PubMed  Google Scholar 

  • Lauber K, Bohn E, Kröber SM, Xiao YJ, Blumenthal SG, Lindemann RK, et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell. 2003;113:717–30.

    Article  CAS  PubMed  Google Scholar 

  • Lin LL, Wartmann M, Lin AY, Knopf JL, Seth A, Davis RJ. cPLA2 is phosphorylated and activated by MAP kinase. Cell. 1993;72:269–78.

    Article  CAS  PubMed  Google Scholar 

  • MacPhee M, Chepenik KP, Liddell RA, Nelson KK, Siracusa LD, Buchberg AM. The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin-induced intestinal neoplasia. Cell. 1995;81:957–66.

    Article  CAS  PubMed  Google Scholar 

  • Mancuso DJ, Kotzbauer P, Wozniak DF, Sims HF, Jenkins CM, Guan S, et al. Genetic ablation of calcium-independent phospholipase A2γ leads to alterations in hippocampal cardiolipin content and molecular species distribution, mitochondrial degeneration, autophagy, and cognitive dysfunction. J Biol Chem. 2009;284:35632–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Miki Y, Yamamoto K, Taketomi Y, Sato H, Shimo K, Kobayashi T, et al. Lymphoid tissue phospholipase A2 group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators. J Exp Med. 2013;210:1217–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Miki Y, Kidoguchi Y, Sato M, Taketomi Y, Taya C, Muramatsu K, et al. Dual roles of group IID phospholipase A2 in inflammation and cancer. J Biol Chem. 2016;291:15588–601.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Morgan NV, Westaway SK, Morton JE, Gregory A, Gissen P, Sonek S, et al. PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. Nat Genet. 2006;38:752–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Muñoz-Sanjuán I, Brivanlou AH. Induction of ectopic olfactory structures and bone morphogenetic protein inhibition by Rossy, a group XII secreted phospholipase A2. Mol Cell Biol. 2005;25:3608–19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Murakami M, Taketomi Y, Girard C, Yamamoto K, Lambeau G. Emerging roles of secreted phospholipase A2 enzymes: lessons from transgenic and knockout mice. Biochimie. 2010;92:561–82.

    Article  CAS  PubMed  Google Scholar 

  • Murakami M, Sato H, Miki Y, Yamamoto K, Taketomi Y. A new era of secreted phospholipase A2. J Lipid Res. 2015;56:1248–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Murase R, Sato H, Yamamoto K, Ushida A, Nishito Y, Ikeda K, et al. Group X secreted phospholipase A2 releases ω3 polyunsaturated fatty acids, suppresses colitis, and promotes sperm fertility. J Biol Chem. 2016;291:6895–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nagase T, Uozumi N, Ishii S, Kume K, Izumi T, Ouchi Y, Shimizu T. Acute lung injury by sepsis and acid aspiration: a key role for cytosolic phospholipase A2. Nat Immunol. 2000;1:42–6.

    Article  CAS  PubMed  Google Scholar 

  • Nicholls SJ, Kastelein JJ, Schwartz GG, Bash D, Rosenson RS, Cavender MA, et al. Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial. JAMA. 2014;311:252–62.

    Article  CAS  PubMed  Google Scholar 

  • Ohta S, Imamura M, Xing W, Boyce JA, Balestrieri B. Group V secretory phospholipase A2 is involved in macrophage activation and is sufficient for macrophage effector functions in allergic pulmonary inflammation. J Immunol. 2013;190:5927–38.

    Article  PubMed  CAS  Google Scholar 

  • Ohto T, Uozumi N, Hirabayashi T, Shimizu T. Identification of novel cytosolic phospholipase A 2s, murine cPLA 2δ, ε, and ζ, which form a gene cluster with cPLA 2β. J Biol Chem. 2005;280:24576–83.

    Article  PubMed  CAS  Google Scholar 

  • Ohtsuki M, Taketomi Y, Arata S, Masuda S, Ishikawa Y, Ishii T, et al. Transgenic expression of group V, but not group X, secreted phospholipase A2 in mice leads to neonatal lethality because of lung dysfunction. J Biol Chem. 2006;281:36420–33.

    Article  CAS  PubMed  Google Scholar 

  • Pernet E, Guillemot L, Burgel PR, Martin C, Lambeau G, Sermet-Gaudelus I, et al. Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity. Nat Commun. 2014;5:5105.

    Article  CAS  PubMed  Google Scholar 

  • Satake Y, Diaz BL, Balestrieri B, Lam BK, Kanaoka Y, Grusby MJ, Arm JP. Role of group V phospholipase A2 in zymosan-induced eicosanoid generation and vascular permeability revealed by targeted gene disruption. J Biol Chem. 2004;279:16488–94.

    Article  PubMed  CAS  Google Scholar 

  • Sato H, Kato R, Isogai Y, Saka G, Ohtsuki M, Taketomi Y, et al. Analyses of group III secreted phospholipase A2 transgenic mice reveal potential participation of this enzyme in plasma lipoprotein modification, macrophage foam cell formation, and atherosclerosis. J Biol Chem. 2008;283:33483–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sato H, Taketomi Y, Isogai Y, Miki Y, Yamamoto K, Masuda S, et al. Group III secreted phospholipase A2 regulates epididymal sperm maturation and fertility in mice. J Clin Invest. 2010;120:1400–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sato H, Taketomi Y, Ushida A, Isogai Y, Kojima T, Hirabayashi T, et al. The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity. Cell Metab. 2014;20:119–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Saunders CJ, Moon SH, Liu X, Thiffault I, Coffman K, LePichon JB, et al. Loss of function variants in human PNPLA8 encoding calcium-independent phospholipase A2 γ recapitulate the mitochondriopathy of the homologous null mouse. Hum Mutat. 2015;36:301–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schewe M, Franken PF, Sacchetti A, Schmitt M, Joosten R, Böttcher R, et al. Secreted phospholipases A2 are intestinal stem cell niche factors with distinct roles in homeostasis, inflammation, and cancer. Cell Stem Cell. 2016;19:38–51.

    Article  CAS  PubMed  Google Scholar 

  • Shinzawa K, Sumi H, Ikawa M, Matsuoka Y, Okabe M, Sakoda S, Tsujimoto Y. Neuroaxonal dystrophy caused by group VIA phospholipase A2 deficiency in mice: a model of human neurodegenerative disease. J Neurosci. 2008;28:2212–20.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Silva-Filho JL, Peruchetti DB, Moraes-Santos F, Landgraf SS, Silva LS, Sirtoli GM, et al. Group V secretory phospholipase A2 is involved in tubular integrity and sodium handling in the kidney. PLoS One. 2016;11:e0147785.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Song H, Wohltmann M, Bao S, Ladenson JH, Semenkovich CF, Turk J. Mice deficient in group VIB phospholipase A2 (iPLA 2γ) exhibit relative resistance to obesity and metabolic abnormalities induced by a western diet. Am J Physiol Endocrinol Metab. 2010;298:E1097–114.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Taketomi Y, Ueno N, Kojima T, Sato H, Murase R, Yamamoto K, et al. Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis. Nat Immunol. 2013;14:554–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tucker DE, Ghosh M, Ghomashchi F, Loper R, Suram S, John BS, et al. Role of phosphorylation and basic residues in the catalytic domain of cytosolic phospholipase A 2α in regulating interfacial kinetics and binding and cellular function. J Biol Chem. 2009;284:9596–611.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Uozumi N, Kume K, Nagase T, Nakatani N, Ishii S, Tashiro F, et al. Role of cytosolic phospholipase A2 in allergic response and parturition. Nature. 1997;390:618–22.

    Article  PubMed  CAS  Google Scholar 

  • Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, et al. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science. 2006;312:1220–3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vijay R, Hua X, Meyerholz DK, Miki Y, Yamamoto K, Gelb M, et al. Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection. J Exp Med. 2015;212:1851–68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Weinrauch Y, Abad C, Liang NS, Lowry SF, Weiss J. Mobilization of potent plasma bactericidal activity during systemic bacterial challenge. Role of group IIA phospholipase A2. J Clin Invest. 1998;102:633–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yamamoto K, Miki Y, Sato M, Taketomi Y, Nishito Y, Taya C, et al. The role of group IIF-secreted phospholipase A2 in epidermal homeostasis and hyperplasia. J Exp Med. 2015;212:1901–19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yamamoto K, Miki Y, Sato H, Nishito Y, Gelb MH, Taketomi Y, Murakami M. Expression and function of group IIE phospholipase A2 in mouse skin. J Biol Chem. 2016;291:15602–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhou Q, Yen A, Rymarczyk G, Asai H, Trengrove C, Aziz N, et al. Impairment of PARK14-dependent Ca2+ signalling is a novel determinant of Parkinson’s disease. Nat Commun. 2016;7:10332.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

This work was supported by AMED-CREST and JSPS KAKENHI (16H02613 and 15H05905).

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Correspondence to Makoto Murakami .

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Murakami, M. (2018). Phospholipase A2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_97

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