The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PLA2G2A  -  phospholipase A2, group IIA (platelets,...

Homo sapiens

Synonyms: GIIC sPLA2, Group IIA phospholipase A2, MOM1, NPS-PLA2, Non-pancreatic secretory phospholipase A2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PLA2G2A

  • Beyond its potential diagnostic and prognostic significance, this result suggests the intriguing possibility that the activity of PLA2G2A may suppress progression or metastasis of human gastric cancer [1].
  • Additional genes involved in osteoclastogenesis and bone resorption, which were statistically different, include annexin 2, SMAD, PLA2G2A, and TGFbeta1 [2].
  • To test the hypothesis of a correlation between PLA2G2A gene alterations and human tumor development, we screened 14 patients with FAP and 20 patients with sporadic colorectal cancer for germline and somatic PLA2G2A gene mutations [3].
  • Invading bacteria such as Staphylococcus aureus induce mobilization of professional phagocytes (e.g., neutrophils) and extracellular antibacterial proteins (e.g., group IIA phospholipase A2 (gIIA PLA2)) [4].
  • Incubation with pertussis toxin prior to the addition of either sPLA2 or LPA only showed abrogation of the response to LPA, thus suggesting the involvement of pertussis-sensitive Gi-proteins in the case of LPA [5].

Psychiatry related information on PLA2G2A


High impact information on PLA2G2A

  • SPH hydrolysis, which is provoked by various cytokines, regulates sPLA2 activity, and the novel lipid mediator LPA can be generated by this pathway [10].
  • We conclude that PLA2/5-lipoxygenase-mediated leukotriene C4 production constitutes a novel and specific signal transduction pathway in growth factor action [11].
  • We report the cloning and expression of a cDNA encoding a high molecular weight (85.2 kd) cytosolic phospholipase A2 (cPLA2) that has no detectable sequence homology with the secreted forms of PLA2 [12].
  • Phospholipase A2 (PLA2) enzymes are critical regulators of prostaglandin and leukotriene synthesis and can directly modify the composition of cellular membranes [13].
  • Here we report the refined, three-dimensional crystal structure at 2.2 A resolution of recombinant human rheumatoid arthritic synovial fluid PLA2 [14].

Chemical compound and disease context of PLA2G2A


Biological context of PLA2G2A

  • Expression of PLA2G2A, a gene previously implicated as a modifier of the Apc(Min/+) (multiple intestinal neoplasia 1) mutant phenotype in the mouse, was significantly correlated with patient survival [1].
  • The Group IIA phospholipase gene (PLA2G2A) protein coding regions exhibit significant homology with recently described Group IIC (PLA2G2C) and Group V (PLA2GV) genes [19].
  • Accumulation of gIIA PLA2 in inflammatory fluids confers potent extracellular antistaphylococcal activity and at lower concentrations promotes bacterial phospholipid degradation during phagocytosis of S. aureus by human neutrophils [4].
  • D-alanylation of (lipo) teichoic acids of S. aureus increases bacterial resistance to gIIA PLA2 approximately 100-fold, raising the possibility that the resistance of ingested S. aureus to related gV and gX secretory PLA2 present in human neutrophil granules depends on D-alanylation mediated by the dlt operon [4].
  • Phospholipase A2 (PLA2) proteins affect cellular activation, signal transduction, and possibly innate immunity [20].

Anatomical context of PLA2G2A

  • The extreme potency of the gIIA PLA2 toward dltA S. aureus suggests that even small amounts of this extracellular enzyme mobilized early in inflammation could contribute substantially to the overall cytotoxicity of acute inflammatory exudates toward S. aureus when D-alanylation of (lipo)teichoic acids is limiting [4].
  • Synergistic effect of interleukin-1 beta and tumor necrosis factor alpha on PGE2 production by articular chondrocytes does not involve PLA2 stimulation [21].
  • There was no cross-reactivity with other (secretory) isoforms of PLA2 (sPLA2 types I-III) either from porcine pancreas, human synovial fluid, or bee venom [22].
  • Phospholipase A2 (PLA2) activities in rheumatoid synovial fibroblasts (RSF) stimulated with interleukin-1 beta (IL-1 beta) were investigated [23].
  • IL-1 beta treatment did not increase the level of secretory PLA2 (sPLA2) activity or sPLA2 protein in the conditioned medium or subcellular fractions of lysed RSF [23].

Associations of PLA2G2A with chemical compounds

  • The purpose of this study was to define the role of secretory phospholipase A2 (sPLA2), calcium-independent PLA2, and cytosolic PLA2 (cPLA2) in arachidonic acid (AA) release from fMLP-stimulated human neutrophils [24].
  • Treatments with inhibitors of the catalytic effect of sPLA2 such as p-bromophenacyl bromide and dithiothreitol did not prevent the effect on cPLA2 activation [5].
  • In contrast, preincubation of 1321N1 cells with the antagonist of the sPLA2 receptor p-aminophenyl-alpha-D-mannopyranoside-bovine serum albumin, blocked cPLA2 activation with a EC50 similar to that described for the inhibition of binding of sPLA2 to its receptor [5].
  • In contrast, IL-1-induced sPLA2 gene expression determined in the same cell samples was weak and most often rapid, and dexamethasone further stimulated it [25].
  • (2) cPLA2 is active at nM calcium (Ca2+) concentrations; sPLA2 requires microM Ca2+ levels [26].

Physical interactions of PLA2G2A


Regulatory relationships of PLA2G2A

  • In an attempt to investigate early molecular events in CD69-mediated cell activation we studied the relative contribution of phospholipase A2 (PLA2) and phosphatidylinositol-specific phospholipase C-dependent pathways during platelet activation induced by CD69 stimulation [29].
  • Moreover, maximum sPLA2 levels induced by IL-2 were higher in patients who had progressive disease after therapy than in patients who had stable disease or a partial response [30].
  • TNF-induced NF-kappaB activation was also strongly reduced in cells stimulated in the presence of the secretory PLA2 (sPLA2) inhibitors 12-epi-scalaradial and LY311727 [31].
  • As sPLA2 requires Ca2+ for activity, these results indicate that both Ca2+ mobilization and cPLA2 activation induced by sPLA2 are unrelated to phospholipase activity but dependent on signaling mechanisms [18].
  • The non-proteinaceous polycationic hexadimethrine and acidic protein casein failed to inhibit platelet sPLA2 activity [32].

Other interactions of PLA2G2A

  • RESULTS: Expression of PLA2G2A and PLA2G5, the main placenta phospholipases, was greater (P < 0.05) in placenta of obese compared with control neonates and was associated with increased 20:3 and 20:5 omega-3 polyunsaturated fatty acids [33].
  • The genes PLA2G2A (1p35.1-36) and TP73 (1p36.3) were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss [34].
  • Moreover, treatment of 1321N1 cells with the MAP kinase kinase inhibitor PD-98059 inhibited the activation of both cPLA2 and p42 MAP kinase produced by sPLA2 [5].
  • In contrast, 14 kDa, secreted PLA2 (sPLA2), which was also produced by RSF, was not affected by IL-1 beta treatment [35].
  • HVSMC contained mRNA encoding both the secreted and cytosolic forms of phospholipase A2 (sPLA2 and cPLA2, respectively) [36].

Analytical, diagnostic and therapeutic context of PLA2G2A

  • The mRNA levels of cPLA2, sPLA2, and COX-2 were also measured by Northern blotting, using specific complementary DNA probes [21].
  • Synovial fluid from arthritic patients contains multiple forms of phospholipase A2 (PLA2), as resolved by high performance liquid chromatography (Seilhamer, J.J., Plant, S., Pruzanski, W., Schilling, J., Stefanski, E., Vadas, P., and Johnson, L. K. (1989) J. Biochem. (Tokyo), submitted for publication) [37].
  • To date, there are very limited data on PLA2 protein by Western blotting after cerebral ischemia, though some immunohistochemical studies (for cPLA2 and sPLA2) have been reported [38].
  • Bone marrow transplantation to LDL receptor-deficient mice was performed to study sPLA2 IIa in atherosclerosis [39].
  • Cacospongionolide B, that is bioavailable when is given orally, reduced the elevated levels of sPLA2 present in paw homogenates of rats with adjuvant arthritis [40].


  1. Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis. Leung, S.Y., Chen, X., Chu, K.M., Yuen, S.T., Mathy, J., Ji, J., Chan, A.S., Li, R., Law, S., Troyanskaya, O.G., Tu, I.P., Wong, J., So, S., Botstein, D., Brown, P.O. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. An expression signature classifies chemotherapy-resistant pediatric osteosarcoma. Mintz, M.B., Sowers, R., Brown, K.M., Hilmer, S.C., Mazza, B., Huvos, A.G., Meyers, P.A., Lafleur, B., McDonough, W.S., Henry, M.M., Ramsey, K.E., Antonescu, C.R., Chen, W., Healey, J.H., Daluski, A., Berens, M.E., Macdonald, T.J., Gorlick, R., Stephan, D.A. Cancer Res. (2005) [Pubmed]
  3. Loss of the PLA2G2A gene in a sporadic colorectal tumor of a patient with a PLA2G2A germline mutation and absence of PLA2G2A germline alterations in patients with FAP. Nimmrich, I., Friedl, W., Kruse, R., Pietsch, S., Hentsch, S., Deuter, R., Winde, G., Müller, O. Hum. Genet. (1997) [Pubmed]
  4. Effect of D-alanylation of (lipo)teichoic acids of Staphylococcus aureus on host secretory phospholipase A2 action before and after phagocytosis by human neutrophils. Hunt, C.L., Nauseef, W.M., Weiss, J.P. J. Immunol. (2006) [Pubmed]
  5. Secretory phospholipase A2 activates the cascade of mitogen-activated protein kinases and cytosolic phospholipase A2 in the human astrocytoma cell line 1321N1. Hernández, M., Burillo, S.L., Crespo, M.S., Nieto, M.L. J. Biol. Chem. (1998) [Pubmed]
  6. Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases. Sun, G.Y., Xu, J., Jensen, M.D., Simonyi, A. J. Lipid Res. (2004) [Pubmed]
  7. Are disturbances in lipid-protein interactions by phospholipase-A2 a predisposing factor in affective illness? Hibbeln, J.R., Palmer, J.W., Davis, J.M. Biol. Psychiatry (1989) [Pubmed]
  8. Elevated PLA2 activity in schizophrenics and other psychiatric patients. Noponen, M., Sanfilipo, M., Samanich, K., Ryer, H., Ko, G., Angrist, B., Wolkin, A., Duncan, E., Rotrosen, J. Biol. Psychiatry (1993) [Pubmed]
  9. Modulation of phospholipases A2 and C activities against dilauroylphosphorylcholine in mixed monolayers with semisynthetic derivatives of ganglioside and sphingosine. Perillo, M.A., Guidotti, A., Costa, E., Yu, R.K., Maggio, B. Mol. Membr. Biol. (1994) [Pubmed]
  10. Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Fourcade, O., Simon, M.F., Viodé, C., Rugani, N., Leballe, F., Ragab, A., Fournié, B., Sarda, L., Chap, H. Cell (1995) [Pubmed]
  11. Epidermal growth factor activates calcium channels by phospholipase A2/5-lipoxygenase-mediated leukotriene C4 production. Peppelenbosch, M.P., Tertoolen, L.G., den Hertog, J., de Laat, S.W. Cell (1992) [Pubmed]
  12. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. Clark, J.D., Lin, L.L., Kriz, R.W., Ramesha, C.S., Sultzman, L.A., Lin, A.Y., Milona, N., Knopf, J.L. Cell (1991) [Pubmed]
  13. Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2. Bonventre, J.V., Huang, Z., Taheri, M.R., O'Leary, E., Li, E., Moskowitz, M.A., Sapirstein, A. Nature (1997) [Pubmed]
  14. Structure of recombinant human rheumatoid arthritic synovial fluid phospholipase A2 at 2.2 A resolution. Wery, J.P., Schevitz, R.W., Clawson, D.K., Bobbitt, J.L., Dow, E.R., Gamboa, G., Goodson, T., Hermann, R.B., Kramer, R.M., McClure, D.B. Nature (1991) [Pubmed]
  15. Phospholipase A2 activating protein and idiopathic inflammatory bowel disease. Peterson, J.W., Dickey, W.D., Saini, S.S., Gourley, W., Klimpel, G.R., Chopra, A.K. Gut (1996) [Pubmed]
  16. Adenosine Regulation of Cystic Fibrosis Transmembrane Conductance Regulator through Prostenoids in Airway Epithelia. Li, Y., Wang, W., Parker, W., Clancy, J.P. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  17. Effects of phospholipase A2, free fatty acids and 2-lysolecithin on the crystallization of cholesterol in gallbladder bile. Schöne, A., Jüngst, D., Meyer, G., Hernandez-Richter, T., Fischer, S. Eur. J. Clin. Invest. (2000) [Pubmed]
  18. Secretory phospholipase A2 induces phospholipase Cgamma-1 activation and Ca2+ mobilization in the human astrocytoma cell line 1321N1 by a mechanism independent of its catalytic activity. Hernández, M., Barrero, M.J., Alvarez, J., Montero, M., Sánchez Crespo, M., Nieto, M.L. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  19. Low-molecular-weight, calcium-dependent phospholipase A2 genes are linked and map to homologous chromosome regions in mouse and human. Tischfield, J.A., Xia, Y.R., Shih, D.M., Klisak, I., Chen, J., Engle, S.J., Siakotos, A.N., Winstead, M.V., Seilhamer, J.J., Allamand, V., Gyapay, G., Lusis, A.J. Genomics (1996) [Pubmed]
  20. Lysis of human immunodeficiency virus type 1 by a specific secreted human phospholipase A2. Kim, J.O., Chakrabarti, B.K., Guha-Niyogi, A., Louder, M.K., Mascola, J.R., Ganesh, L., Nabel, G.J. J. Virol. (2007) [Pubmed]
  21. Synergistic effect of interleukin-1 beta and tumor necrosis factor alpha on PGE2 production by articular chondrocytes does not involve PLA2 stimulation. Berenbaum, F., Jacques, C., Thomas, G., Corvol, M.T., Béréziat, G., Masliah, J. Exp. Cell Res. (1996) [Pubmed]
  22. Quantitation of the cytosolic phospholipase A2 (type IV) in isolated human peripheral blood eosinophils by sandwich-ELISA. Zhu, X., Muñoz, N.M., Rubio, N., Herrnreiter, A., Mayer, D., Douglas, I., Leff, A.R. J. Immunol. Methods (1996) [Pubmed]
  23. Interleukin-1 beta stimulates cytosolic phospholipase A2 in rheumatoid synovial fibroblasts. Hulkower, K.I., Hope, W.C., Chen, T., Anderson, C.M., Coffey, J.W., Morgan, D.W. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  24. Involvement of cytosolic phospholipase A2 and secretory phospholipase A2 in arachidonic acid release from human neutrophils. Marshall, J., Krump, E., Lindsay, T., Downey, G., Ford, D.A., Zhu, P., Walker, P., Rubin, B. J. Immunol. (2000) [Pubmed]
  25. Interleukin-1-induced prostaglandin E2 biosynthesis in human synovial cells involves the activation of cytosolic phospholipase A2 and cyclooxygenase-2. Angel, J., Berenbaum, F., Le Denmat, C., Nevalainen, T., Masliah, J., Fournier, C. Eur. J. Biochem. (1994) [Pubmed]
  26. Activation of cytosolic phospholipase A2 in permeabilized human neutrophils. Bauldry, S.A., Wooten, R.E., Bass, D.A. Biochim. Biophys. Acta (1996) [Pubmed]
  27. Identification of an autoantigen on the surface of apoptotic human T cells as a new protein interacting with inflammatory group IIA phospholipase A2. Boilard, E., Bourgoin, S.G., Bernatchez, C., Surette, M.E. Blood (2003) [Pubmed]
  28. Type II secretory phospholipase A2 binds to ischemic flip-flopped cardiomyocytes and subsequently induces cell death. Nijmeijer, R., Willemsen, M., Meijer, C.J., Visser, C.A., Verheijen, R.H., Gottlieb, R.A., Hack, C.E., Niessen, H.W. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  29. Preferential involvement of a phospholipase A2-dependent pathway in CD69-mediated platelet activation. Testi, R., Pulcinelli, F.M., Cifone, M.G., Botti, D., Del Grosso, E., Riondino, S., Frati, L., Gazzaniga, P.P., Santoni, A. J. Immunol. (1992) [Pubmed]
  30. Therapy with interleukin-2 induces the systemic release of phospholipase-A2. Wolbink, G.J., Schalkwijk, C., Baars, J.W., Wagstaff, J., van den Bosch, H., Hack, C.E. Cancer Immunol. Immunother. (1995) [Pubmed]
  31. Selective inhibitors of cytosolic or secretory phospholipase A2 block TNF-induced activation of transcription factor nuclear factor-kappa B and expression of ICAM-1. Thommesen, L., Sjursen, W., Gåsvik, K., Hanssen, W., Brekke, O.L., Skattebøl, L., Holmeide, A.K., Espevik, T., Johansen, B., Laegreid, A. J. Immunol. (1998) [Pubmed]
  32. Reversible inhibition by protamine of human synovial and rabbit platelet secretory phospholipase A2. Emadi, S., Elalamy, I., Vargaftig, B.B., Hatmi, M. Biochim. Biophys. Acta (1996) [Pubmed]
  33. Activation of phospholipase A2 is associated with generation of placental lipid signals and fetal obesity. Varastehpour, A., Radaelli, T., Minium, J., Ortega, H., Herrera, E., Catalano, P., Hauguel-de Mouzon, S. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  34. Evaluation of 1p losses in primary carcinomas, local recurrences and peripheral metastases from colorectal cancer patients. Thorstensen, L., Qvist, H., Heim, S., Liefers, G.J., Nesland, J.M., Giercksky, K.E., Lothe, R.A. Neoplasia (2000) [Pubmed]
  35. Interleukin-1 beta induces cytosolic PLA2 in parallel with prostaglandin E2 in rheumatoid synovial fibroblasts. Hulkower, K.I., Coffey, J.W., Levin, W., Anderson, C.M., Chen, T., Hope, W.C., Bolin, D.R., Morgan, D.W. Agents Actions (1993) [Pubmed]
  36. COX-2 and cytosolic PLA2 mediate IL-1beta-induced cAMP production in human vascular smooth muscle cells. Beasley, D. Am. J. Physiol. (1999) [Pubmed]
  37. Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid. Seilhamer, J.J., Pruzanski, W., Vadas, P., Plant, S., Miller, J.A., Kloss, J., Johnson, L.K. J. Biol. Chem. (1989) [Pubmed]
  38. Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Muralikrishna Adibhatla, R., Hatcher, J.F. Free Radic. Biol. Med. (2006) [Pubmed]
  39. Macrophage-specific overexpression of group IIa sPLA2 increases atherosclerosis and enhances collagen deposition. Ghesquiere, S.A., Gijbels, M.J., Anthonsen, M., van Gorp, P.J., van der Made, I., Johansen, B., Hofker, M.H., de Winther, M.P. J. Lipid Res. (2005) [Pubmed]
  40. Modulation of acute and chronic inflammatory processes by cacospongionolide B, a novel inhibitor of human synovial phospholipase A2. García Pastor, P., De Rosa, S., De Giulio, A., Payá, M., Alcaraz, M.J. Br. J. Pharmacol. (1999) [Pubmed]
WikiGenes - Universities