Gene Symbol: PLA2G4A
Description: phospholipase A2 group IVA
Alias: PLA2G4, cPLA2, cPLA2-alpha, cytosolic phospholipase A2, calcium-dependent phospholipid-binding protein, lysophospholipase, phosphatidylcholine 2-acylhydrolase, phospholipase A2, group IVA (cytosolic, calcium-dependent)
Species: human
Products:     PLA2G4A

Top Publications

  1. Clark J, Lin L, Kriz R, Ramesha C, Sultzman L, Lin A, et al. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. Cell. 1991;65:1043-51 pubmed
    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...
  2. Lin L, Wartmann M, Lin A, Knopf J, Seth A, Davis R. cPLA2 is phosphorylated and activated by MAP kinase. Cell. 1993;72:269-78 pubmed
    ..that stimulate the release of arachidonic acid causes increased serine phosphorylation and activation of cytosolic phospholipase A2 (cPLA2). Here we report that cPLA2 is a substrate for mitogen-activated protein (MAP) kinase...
  3. Girotti M, Evans J, Burke D, Leslie C. Cytosolic phospholipase A2 translocates to forming phagosomes during phagocytosis of zymosan in macrophages. J Biol Chem. 2004;279:19113-21 pubmed
    ..The results demonstrate that cPLA(2)alpha targets the phagosome membrane, which may serve as a source of arachidonic acid for eicosanoid production. ..
  4. Pawliczak R, Logun C, Madara P, Lawrence M, Woszczek G, Ptasinska A, et al. Cytosolic phospholipase A2 Group IValpha but not secreted phospholipase A2 Group IIA, V, or X induces interleukin-8 and cyclooxygenase-2 gene and protein expression through peroxisome proliferator-activated receptors gamma 1 and 2 in human lung cells. J Biol Chem. 2004;279:48550-61 pubmed
    ..We have shown previously that cytosolic phospholipase A2 (cPLA2) is able to activate gene expression through PPAR-gamma response elements (Pawliczak, R., Han, C...
  5. Parhamifar L, Jeppsson B, Sjölander A. Activation of cPLA2 is required for leukotriene D4-induced proliferation in colon cancer cells. Carcinogenesis. 2005;26:1988-98 pubmed
    ..The present data reveal that cPLA(2)alpha, an important intracellular signal activated by inflammatory mediators, is an important regulator of colon tumor growth. ..
  6. Casas J, Gijón M, Vigo A, Crespo M, Balsinde J, Balboa M. Phosphatidylinositol 4,5-bisphosphate anchors cytosolic group IVA phospholipase A2 to perinuclear membranes and decreases its calcium requirement for translocation in live cells. Mol Biol Cell. 2006;17:155-62 pubmed
    ..PtdIns(4,5)P2 anchors the enzyme to perinuclear membranes and allows for a proper interaction with its phospholipid substrate to release arachidonic acid. ..
  7. Prevost N, Mitsios J, Kato H, Burke J, Dennis E, Shimizu T, et al. Group IVA cytosolic phospholipase A2 (cPLA2alpha) and integrin alphaIIbbeta3 reinforce each other's functions during alphaIIbbeta3 signaling in platelets. Blood. 2009;113:447-57 pubmed publisher
    ..This provides a plausible explanation for the role of alphaIIbbeta3 in TxA(2) formation and in the defective hemostatic function of mouse or human platelets deficient in cPLA(2)alpha. ..
  8. Tucker D, Ghosh M, Ghomashchi F, Loper R, Suram S, John B, et al. Role of phosphorylation and basic residues in the catalytic domain of cytosolic phospholipase A2alpha in regulating interfacial kinetics and binding and cellular function. J Biol Chem. 2009;284:9596-611 pubmed publisher
    ..The results demonstrate that Ser-505 phosphorylation and basic residues in the catalytic domain principally act to regulate cPLA(2)alpha hydrolytic activity. ..
  9. Sharp J, Pickard R, Chiou X, Manetta J, Kovacevic S, Miller J, et al. Serine 228 is essential for catalytic activities of 85-kDa cytosolic phospholipase A2. J Biol Chem. 1994;269:23250-4 pubmed
    The Ca(2+)-sensitive cytosolic phospholipase A2 (cPLA2) displays both a phospholipase A2 and a lysophospholipase activity...

More Information

Publications123 found, 100 shown here

  1. Regan Klapisz E, Krouwer V, Langelaar Makkinje M, Nallan L, Gelb M, Gerritsen H, et al. Golgi-associated cPLA2alpha regulates endothelial cell-cell junction integrity by controlling the trafficking of transmembrane junction proteins. Mol Biol Cell. 2009;20:4225-34 pubmed publisher
  2. San Pietro E, Capestrano M, Polishchuk E, DiPentima A, Trucco A, Zizza P, et al. Group IV phospholipase A(2)alpha controls the formation of inter-cisternal continuities involved in intra-Golgi transport. PLoS Biol. 2009;7:e1000194 pubmed publisher
    ..These findings identify cPLA(2)alpha as the first component of the machinery that is responsible for the formation of intercisternal tubular continuities and support a role for these continuities in transport through the Golgi complex...
  3. Walters J, Bickford J, Beachy D, Newsom K, Herlihy J, Peck M, et al. cPLA(2)? gene activation by IL-1? is dependent on an upstream kinase pathway, enzymatic activation and downstream 15-lipoxygenase activity: a positive feedback loop. Cell Signal. 2011;23:1944-51 pubmed publisher
    ..Overall, these data support an MKK3/MKK6?p38 MAPK?MSK-1?cPLA(2)??15-LOX2-dependent, positive feedback loop where a protein's enzymatic activity is required to regulate its own gene induction by a pro-inflammatory stimulus. ..
  4. Pickard R, Chiou X, Strifler B, DeFelippis M, Hyslop P, Tebbe A, et al. Identification of essential residues for the catalytic function of 85-kDa cytosolic phospholipase A2. Probing the role of histidine, aspartic acid, cysteine, and arginine. J Biol Chem. 1996;271:19225-31 pubmed
    b>Cytosolic phospholipase A2 (cPLA2) hydrolyzes the sn-2-acyl ester bond of phospholipids and shows a preference for arachidonic acid-containing substrates...
  5. Osterström A, Dimberg J, Fransen K, Söderkvist P. Expression of cytosolic and group X secretory phospholipase A(2) genes in human colorectal adenocarcinomas. Cancer Lett. 2002;182:175-82 pubmed
    ..Moreover, our results cannot consistently reflect an overexpression of sPLA(2)-X gene in colorectal cancer tissues. ..
  6. Grewal S, Morrison E, Ponnambalam S, Walker J. Nuclear localisation of cytosolic phospholipase A2-alpha in the EA.hy.926 human endothelial cell line is proliferation dependent and modulated by phosphorylation. J Cell Sci. 2002;115:4533-43 pubmed
  7. Herbert S, Odell A, Ponnambalam S, Walker J. The confluence-dependent interaction of cytosolic phospholipase A2-alpha with annexin A1 regulates endothelial cell prostaglandin E2 generation. J Biol Chem. 2007;282:34468-78 pubmed
    ..Thus the confluence-dependent interaction of cPLA(2)alpha and annexin A1 at the Golgi acts as a novel molecular switch controlling cPLA(2)alpha activity and endothelial cell prostaglandin generation. ..
  8. Umeno J, Matsumoto T, Esaki M, Kukita Y, Tahira T, Yanaru Fujisawa R, et al. Impact of group IVA cytosolic phospholipase A2 gene polymorphisms on phenotypic features of patients with familial adenomatous polyposis. Int J Colorectal Dis. 2010;25:293-301 pubmed publisher
    ..4; 95% CI, 1.2-64.2; p = 0.027). The cPLA ( 2 )alpha gene may be a possible disease modifier gene in FAP. ..
  9. Nakatani Y, Tanioka T, Sunaga S, Murakami M, Kudo I. Identification of a cellular protein that functionally interacts with the C2 domain of cytosolic phospholipase A(2)alpha. J Biol Chem. 2000;275:1161-8 pubmed
    ..These results suggest that vimentin is an adaptor for cPLA(2)alpha to function properly during the eicosanoid-biosynthetic process. ..
  10. Das S, Rafter J, Kim K, Gygi S, Cho W. Mechanism of group IVA cytosolic phospholipase A(2) activation by phosphorylation. J Biol Chem. 2003;278:41431-42 pubmed
    Group IVA cytosolic phospholipase A2 (cPLA2) has been shown to play a critical role in the agonist-induced release of arachidonic acid...
  11. Gubern A, Casas J, Barceló Torns M, Barneda D, de la Rosa X, Masgrau R, et al. Group IVA phospholipase A2 is necessary for the biogenesis of lipid droplets. J Biol Chem. 2008;283:27369-82 pubmed publisher
  12. Lim S, Cho H, Lee T, Choi C, Min Y, Kim S, et al. Impacts of cytosolic phospholipase A2, 15-prostaglandin dehydrogenase, and cyclooxygenase-2 expressions on tumor progression in colorectal cancer. Yonsei Med J. 2010;51:692-9 pubmed publisher cyclooxygenase-2 (COX-2) which is related to prostaglandin E2 synthesis, other enzymes such as cytosolic phospholipase A2 (cPLA2), microsomal prostaglandin E2 synthase-1 (mPGES-1), and 15-prostaglandin dehydrogenase (15-PGDH) ..
  13. Kisslov L, Hadad N, Rosengraten M, Levy R. HT-29 human colon cancer cell proliferation is regulated by cytosolic phospholipase A(2)? dependent PGE(2)via both PKA and PKB pathways. Biochim Biophys Acta. 2012;1821:1224-34 pubmed publisher
    ..PGE(2)via EP induces CREB phosphorylation by the PKA pathway and regulates ?-catenin and cyclin D1 cellular localization by PKB/Akt pathway. ..
  14. Bao Y, Wang S, Yang X, Li T, Xia Y, Meng X. Metabolomic study of the intervention effects of Shuihonghuazi Formula, a Traditional Chinese Medicinal formulae, on hepatocellular carcinoma (HCC) rats using performance HPLC/ESI-TOF-MS. J Ethnopharmacol. 2017;198:468-478 pubmed publisher
    ..therapeutic effects of SHHZF on liver cancer by adjusting the activities of PE N-methyl transferase (PEMT), Lysophospholipase D, methylenetetrahydrofolate reductase (MTHFR) and lysophospholipase was elucidated by the method of ..
  15. Sato A, Nakazawa K, Sugawara A, Yamazaki Y, Ebina K. The interaction of β2-glycoprotein I with lysophosphatidic acid in platelet aggregation and blood clotting. Biochim Biophys Acta Proteins Proteom. 2018;1866:1232-1241 pubmed publisher
    ..serum, both of which are known to accumulate LPA by the action of lecithin-cholesterol acyltransferase and lysophospholipase D/autotaxin...
  16. Son C, Haines B, Luch A, Ryu C. Identification of the transgenic integration site in 2C T cell receptor transgenic mice. Transgenic Res. 2018;27:441-450 pubmed publisher
    ..Further genomic analysis revealed cytosolic phospholipase A2 group IVA (cPLA2) as the nearest gene to the integration site...
  17. Topaloglu A, Lomniczi A, Kretzschmar D, Dissen G, Kotan L, McArdle C, et al. Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome. J Clin Endocrinol Metab. 2014;99:E2067-75 pubmed publisher
    ..families carrying loss-of-function mutations in PNPLA6, which encodes neuropathy target esterase (NTE), a lysophospholipase that maintains intracellular phospholipid homeostasis by converting lysophosphatidylcholine to ..
  18. Gdula Argasińska J, Czepiel J, Totoń Żurańska J, Jurczyszyn A, Perucki W, Wołkow P. Docosahexaenoic acid regulates gene expression in HUVEC cells treated with polycyclic aromatic hydrocarbons. Toxicol Lett. 2015;236:75-81 pubmed publisher
    ..S transferase Mu1 (GSTM1) protein expression as well as on the prostaglandin synthase 2 (PTGS2), AHR, GSTM1, PLA2G4A, and cytochrome P450 CYP1A1 gene expression...
  19. Jiao Y, Jin D, Jiang F, Liu J, Qu L, Ni W, et al. Characterization and proteomic profiling of pancreatic cancer-derived serum exosomes. J Cell Biochem. 2019;120:988-999 pubmed publisher
    ..Our data provided a basic foundation for further studies on the protein composition of PC-derived exosomes and its involvement in PC biology. ..
  20. Law S, Chan M, Marathe G, Parveen F, Chen C, Ke L. An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases. Int J Mol Sci. 2019;20: pubmed publisher
    ..Hydrolysis of LPC by autotaxin, an enzyme with lysophospholipase D activity, generates lysophosphatidic acid, which is highly associated with cancers...
  21. Wang H, Edwards G, Garzón C, Piqueras C, Bhattacharya S. Aqueous humor phospholipids of DBA/2J and DBA/2J-Gpnmb(+)/SjJ mice. Biochimie. 2015;113:59-68 pubmed publisher
    ..Commensurate with reduced level of lysophospholipids, we found an increased level of lysophospholipase D (Autotaxin) in the hypertensive state. The difference of total phospholipids between young and old was 35...
  22. Cates J, Memoli V, Gonzalez R. Cell cycle and apoptosis regulatory proteins, proliferative markers, cell signaling molecules, CD209, and decorin immunoreactivity in low-grade myxofibrosarcoma and myxoma. Virchows Arch. 2015;467:211-6 pubmed publisher
    ..proliferative markers (KI67, MCM2, phospho-histone H3, and geminin), cell signalling molecules (c-Myc, EGF, EGFR, PLA2G4A, and HSP90), a dendritic cell marker (CD209), and the extracellular matrix proteoglycan decorin...
  23. Crookenden M, Walker C, Heiser A, Murray A, Dukkipati V, Kay J, et al. Effects of precalving body condition and prepartum feeding level on gene expression in circulating neutrophils. J Dairy Sci. 2017;100:2310-2322 pubmed publisher
    ..effect on gene expression; for example, increased expression of genes involved in leukotriene synthesis (PLA2G4A and ALOX5AP) occurred only at 1 wk postcalving in cows overfed (125% of requirements) precalving compared with ..
  24. Qing X, Zeng D, Wang H, Ni X, Lai J, Liu L, et al. Analysis of hepatic transcriptome demonstrates altered lipid metabolism following Lactobacillus johnsonii BS15 prevention in chickens with subclinical necrotic enteritis. Lipids Health Dis. 2018;17:93 pubmed publisher
    ..Besides, suppression of phospholipase A2 group IVA (PLA2G4A) in arachidonic acid metabolism was observed in SNE chickens after BS15 prevention...
  25. Verma A, Panigrahi M, Baba N, Sulabh S, Sadam A, Parida S, et al. Differential expression of ten candidate genes regulating prostaglandin action in reproductive tissues of buffalo during estrous cycle and pregnancy. Theriogenology. 2018;105:7-14 pubmed publisher
    ..However, EP2 and EP3 genes were highly upregulated in pregnancy stage II. The expression of PLA2G4A and PGT genes showed difference in their transcripts in pregnancy, however, the difference was nonsignificant as ..
  26. Singh S, Vennila J, Snijesh V, George G, Sunny C. Implying analytic measures for unraveling rheumatoid arthritis significant proteins through drug target interaction. Interdiscip Sci. 2015;: pubmed
    ..the important hubs which resulted into FOS, KNG1, PTGDS, HSP90AA1, REN, POMC, FCER1G, IL6, ICAM1, SGK1, NOS3 and PLA2G4A. This approach provides an insight to experimental validation of these associations of potential targets for ..
  27. Singh S, Vennila J, Snijesh V, George G, Sunny C. Implying Analytic Measures for Unravelling Rheumatoid Arthritis Significant Proteins Through Drug-Target Interaction. Interdiscip Sci. 2016;8:122-31 pubmed publisher
    ..the important hubs which resulted into FOS, KNG1, PTGDS, HSP90AA1, REN, POMC, FCER1G, IL6, ICAM1, SGK1, NOS3 and PLA2G4A. This approach provides an insight into experimental validation of these associations of potential targets for ..
  28. Hardman C, Chen Y, Salimi M, Jarrett R, Johnson D, Järvinen V, et al. CD1a presentation of endogenous antigens by group 2 innate lymphoid cells. Sci Immunol. 2017;2: pubmed publisher levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-..
  29. Beltrame J, Sordelli M, Cañumil V, Alonso C, Perez Martinez S, Ribeiro M. Steroid hormones induce in vitro human first trimester trophoblast tubulogenesis by the lysophosphatidic acid pathway. Mol Cell Endocrinol. 2018;478:126-132 pubmed publisher
    ..Moreover, sex steroids increased the mRNA levels of the main enzyme that produce lysophosphatidic acid (lysophospholipase-D) but did not regulate LPA3 mRNA levels...
  30. Ge P, Xing N, Ren Y, Zhu L, Han D, Kuang H, et al. Preventive effect of American ginseng against premature ovarian failure in a rat model. Drug Dev Res. 2014;75:521-8 pubmed publisher
    ..b>PLA2G4A expression was positively correlated with POF, while the expression levels of PAPPA, STC2, CCL2, and NELL1 were ..
  31. Sharma A, Meena K, Kanwar S. Molecular characterization and bioinformatics studies of a lipase from Bacillus thermoamylovorans BHK67. Int J Biol Macromol. 2018;107:2131-2140 pubmed publisher
    ..Amino acid characterization of BTL by MALDI-TOF-MS showed considerable resemblance with lysophospholipase L1 related esterase of Lactobacillus ozensis DSM 23829...
  32. Lüschen S, Ussat S, Kronke M, Adam Klages S. Cleavage of human cytosolic phospholipase A2 by caspase-1 (ICE) and caspase-8 (FLICE). Biochem Biophys Res Commun. 1998;253:92-8 pubmed
    ..In a previous study, we have reported that human cPLA2 is proteolytically inactivated during apoptosis through cleavage by a caspase-3-like activity...
  33. Alvarez Guaita A, Vilà de Muga S, Owen D, Williamson D, Magenau A, García Melero A, et al. Evidence for annexin A6-dependent plasma membrane remodelling of lipid domains. Br J Pharmacol. 2015;172:1677-90 pubmed publisher
    ..This study provides the first evidence from live cells that support current models of annexins as membrane organizers. ..
  34. Umeno J, Matsumoto T, Hirano A, Fuyuno Y, Esaki M. Genetic analysis is helpful for the diagnosis of small bowel ulceration. World J Gastroenterol. 2018;24:3198-3200 pubmed publisher
    ..Recently, recessive mutations in the PLA2G4A and SLCO2A1 genes have been shown to cause small intestinal diseases...
  35. Saito K. Reminiscence of phospholipase B in Penicillium notatum. Proc Jpn Acad Ser B Phys Biol Sci. 2014;90:333-46 pubmed
    ..there was a question as to whether it is a single enzyme or a mixture of a phospholipase A2 (PLA2) and a lysophospholipase (LPL)...
  36. Ohkawa R, Kurano M, Mishima Y, Nojiri T, Tokuhara Y, Kishimoto T, et al. Possible involvement of sphingomyelin in the regulation of the plasma sphingosine 1-phosphate level in human subjects. Clin Biochem. 2015;48:690-7 pubmed publisher
    ..acid (LPA) using enzymatic assays, ATX antigen using a two-site enzyme immunoassay, and ATX activity using a lysophospholipase D activity assay...
  37. Hurley B, Pirzai W, Mumy K, Gronert K, McCormick B. Selective eicosanoid-generating capacity of cytoplasmic phospholipase A2 in Pseudomonas aeruginosa-infected epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2011;300:L286-94 pubmed publisher
    ..The therapeutic implications of these findings are significant when considering anti-inflammatory therapies based on targeting eicosanoid synthesis pathways. ..
  38. Guriec N, Le Jossic Corcos C, Simon B, Ianotto J, Tempescul A, Dreano Y, et al. The arachidonic acid-LTB4-BLT2 pathway enhances human B-CLL aggressiveness. Biochim Biophys Acta. 2014;1842:2096-105 pubmed publisher annual proliferation index above 2, over-expressed calcium-dependent and calcium-independent phospholipases A2 (cPLA2-alpha and iPLA2-beta, respectively), 5-lipoxygenase (5LOX) and leukotriene A4 hydroxylase (LTA4H)...
  39. Yang F, Wang M, Zhang B, Xiang W, Zhang K, Chu M, et al. Identification of new progestogen-associated networks in mammalian ovulation using bioinformatics. BMC Syst Biol. 2018;12:36 pubmed publisher
    ..05). This study identified four genes (PGR, RELN, PDE10A and PLA2G4A) by protein-protein interaction networks and pathway analysis, and their functional enrichments were associated ..
  40. Zhou L, Shi M, Zhao L, Lin Z, Tang Z, Sun H, et al. Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis. Parasit Vectors. 2017;10:295 pubmed publisher
    ..b>Lysophospholipase A (LysoPLA), which deacylates lysophospholipids, plays a critical role in mediating the virulence and ..
  41. Hirabayashi T, Murayama T, Shimizu T. Regulatory mechanism and physiological role of cytosolic phospholipase A2. Biol Pharm Bull. 2004;27:1168-73 pubmed
    ..cPLA2gamma is distinct from others in that it is farnesylated and lacks the C2 domain. Biological roles for these new enzymes have not yet been defined. ..
  42. Teo K, Brunton V. The role and therapeutic potential of the autotaxin-lysophosphatidate signalling axis in breast cancer. Biochem J. 2014;463:157-65 pubmed publisher
    ATX (autotaxin) is a secreted lysophospholipase capable of catalysing the formation of the bioactive lipid mediator LPA (lysophosphatidate) from LPC (lysophosphatidylcholine)...
  43. Cheng S, Lin C, Lee I, Hsu C, Kou Y, Yang C. Cigarette smoke extract regulates cytosolic phospholipase A2 expression via NADPH oxidase/MAPKs/AP-1 and p300 in human tracheal smooth muscle cells. J Cell Biochem. 2011;112:589-99 pubmed publisher
    ..These results demonstrated that CSE-induced cPLA(2) expression was mediated through NOX2-dependent p42/p44 MAPK and p38 MAPK/c-Fos and JNK1/2/c-Jun/p300 pathways in HTSMCs. ..
  44. Kita Y, Yoshida K, Tokuoka S, Hamano F, Yamazaki M, Sakimura K, et al. Fever Is Mediated by Conversion of Endocannabinoid 2-Arachidonoylglycerol to Prostaglandin E2. PLoS ONE. 2015;10:e0133663 pubmed publisher
    ..lipase (MGL)-deficient (Mgll-/-) mice, CB1 receptor-MGL compound-deficient (Cnr1-/-Mgll-/-) mice, cytosolic phospholipase A2α (cPLA2α)-deficient (Pla2g4a-/-) mice, and diacylglycerol lipase α (DGLα)-deficient (Dagla-/-..
  45. Wheeler N, Fuss B, Knapp P, Zou S. HIV-1 Tat Inhibits Autotaxin Lysophospholipase D Activity and Modulates Oligodendrocyte Differentiation. ASN Neuro. 2016;8: pubmed
    ..OLGs produce and secrete autotaxin (ATX), an ecto-enzyme containing a lysophospholipase D (lysoPLD) activity that converts lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a lipid ..
  46. Valdes A, Loughlin J, Timms K, van Meurs J, Southam L, Wilson S, et al. Genome-wide association scan identifies a prostaglandin-endoperoxide synthase 2 variant involved in risk of knee osteoarthritis. Am J Hum Genet. 2008;82:1231-40 pubmed publisher
    ..rs4140564 on chromosome 1 mapping 5' to both the PTGS2 and PLA2G4A genes was associated with risk of knee OA in all the cohorts studied (overall odds ratio OR(mh) = 1.55 95% C.I. 1...
  47. Cordeiro Q, Noguti R, Bottino C, Vallada H. Study of association between genetic polymorphisms of phospholipase A2 enzymes and Alzheimer's disease. Arq Neuropsiquiatr. 2010;68:189-93 pubmed
    ..Hence, in the present study, polymorphisms of three genes encoding PLA2 enzymes group (cytosolic PLA2: BanI cPLA2 polymorphism; calcium-independent PLA2: AvrII iPLA2 polymorphism; PAFAH: Val279Phe PAFAH polymorphism) were ..
  48. Valdearcos M, Esquinas E, Meana C, Gil de Gómez L, Guijas C, Balsinde J, et al. Subcellular localization and role of lipin-1 in human macrophages. J Immunol. 2011;186:6004-13 pubmed publisher
    ..Collectively, these data suggest that lipin-1 associates with LDs and regulates the activation of cytosolic group IVA phospholipase A(2)? in human monocyte-derived macrophages. ..
  49. Nadalin S, Giacometti J, Jonovska S, Tomljanović D, Buretic Tomljanovic A. The impact of PLA2G4A and PTGS2 gene polymorphisms, and red blood cell PUFAs deficit on niacin skin flush response in schizophrenia patients. Prostaglandins Leukot Essent Fatty Acids. 2013;88:185-90 pubmed publisher
    ..VNR) and correlated to two functional A/G polymorphisms in genes: phospholipase A2 group IVA (BanI of the PLA2G4A), and rs689466 of the prostaglandin synthase-2 (PTGS2)...
  50. Gdula Argasińska J, Czepiel J, Totoń Żurańska J, Wołkow P, Librowski T, Czapkiewicz A, et al. n-3 Fatty acids regulate the inflammatory-state related genes in the lung epithelial cells exposed to polycyclic aromatic hydrocarbons. Pharmacol Rep. 2016;68:319-28 pubmed publisher
    ..A2 (cPLA2) activity, as well as aryl hydrocarbon receptor (AHR), cytochrome P450 (CYP1A1), phospholipase A2 (PLA2G4A) and prostaglandin synthase 2 (PTGS2) gene expression by qRT-PCR...
  51. Slatter D, Aldrovandi M, O Connor A, Allen S, Brasher C, Murphy R, et al. Mapping the Human Platelet Lipidome Reveals Cytosolic Phospholipase A2 as a Regulator of Mitochondrial Bioenergetics during Activation. Cell Metab. 2016;23:930-44 pubmed publisher
    ..Herein, a lipidomic circuit was uncovered whereby the substrates for this are exclusively provided by cPLA2, including multiple fatty acids and oxidized species that support energy generation via β-oxidation...
  52. Morri H, Ozaki M, Watanabe Y. 5'-flanking region surrounding a human cytosolic phospholipase A2 gene. Biochem Biophys Res Commun. 1994;205:6-11 pubmed
    The 5'-flanking region and the first four exons of a gene encoding human cytosolic phospholipase A2 (cPLA2) were isolated from a human lambda EMBL3 genomic library and sequenced...
  53. Flati V, Haque S, Williams B. Interferon-alpha-induced phosphorylation and activation of cytosolic phospholipase A2 is required for the formation of interferon-stimulated gene factor three. EMBO J. 1996;15:1566-71 pubmed
    Treatment of cells with interferon (IFN)-alpha caused phosphorylation and activation of cytosolic phospholipase A2 (cPLA2). The protein tyrosine kinase Jak1 was found to be necessary for the activation of cPLA2...
  54. Pickard R, Strifler B, Kramer R, Sharp J. Molecular cloning of two new human paralogs of 85-kDa cytosolic phospholipase A2. J Biol Chem. 1999;274:8823-31 pubmed
    Two new cloned human cDNAs encode paralogs of the 85-kDa cytosolic phospholipase A2 (cPLA2). We propose to call these cPLA2beta (114 kDa) and cPLA2gamma (61 kDa), giving the name cPLA2alpha to the well known 85-kDa enzyme...
  55. Bate C, Williams A. Clustering of sialylated glycosylphosphatidylinositol anchors mediates PrP-induced activation of cytoplasmic phospholipase A 2 and synapse damage. Prion. 2012;6:350-3 pubmed publisher
  56. Ayuso P, Plaza Serón M, Doña I, Blanca López N, Campo P, Cornejo García J, et al. Association study of genetic variants in PLA2G4A, PLCG1, LAT, SYK, and TNFRS11A genes in NSAIDs-induced urticaria and/or angioedema patients. Pharmacogenet Genomics. 2015;25:618-21 pubmed publisher
    ..of nine single nucleotide polymorphisms in five genes involved in mast cell activation (SYK, LAT1, PLCG1, PLA2G4A, and TNFRSF11A) in 450 NIUA patients and 500 controls...
  57. Sokolowska M, Borowiec M, Ptasinska A, Cieslak M, Shelhamer J, Kowalski M, et al. 85-kDa cytosolic phospholipase A2 group IValpha gene promoter polymorphisms in patients with severe asthma: a gene expression and case-control study. Clin Exp Immunol. 2007;150:124-31 pubmed
    ..03996) and -185 A allele (P(cor) = 0.03966). These results demonstrate that (CA)(n) and (T)(n) repeats may have an influence on cPLA(2) transcription which might play a role in severe asthma pathogenesis. ..
  58. Görner C, Schrepfer P, Redai V, Wallrapp F, Loll B, Eisenreich W, et al. Identification, characterization and molecular adaptation of class I redox systems for the production of hydroxylated diterpenoids. Microb Cell Fact. 2016;15:86 pubmed publisher
    ..Escherichia coli-based production of the trihydroxylated diterpene cyclooctatin, a potent inhibitor of human lysophospholipase. This production system provides a 43-fold increase in cyclooctatin yield (15 mg/L) compared to the native ..
  59. Szepanowski F, Derksen A, Steiner I, Meyer Zu Hörste G, Daldrup T, Hartung H, et al. Fingolimod promotes peripheral nerve regeneration via modulation of lysophospholipid signaling. J Neuroinflammation. 2016;13:143 pubmed publisher
    ..Furthermore, fingolimod has been reported to reduce LPA synthesis via inhibition of the lysophospholipase autotaxin...
  60. Yatomi Y. [Laboratory-Based Clinical Research I am Aiming for]. Rinsho Byori. 2014;62:1052-5 pubmed
    ..mediator lysophosphatidic acid (LPA), which is produced from lysophosphatidylcholine (LPC) through the lysophospholipase D (lysoPLD) activity of autotaxin (ATX) in body fluids...
  61. Hiller M, Lang C, Michel W, Flieger A. Secreted phospholipases of the lung pathogen Legionella pneumophila. Int J Med Microbiol. 2018;308:168-175 pubmed publisher
    ..Among these are a large variety of lipolytic enzymes which possess phospholipase/lysophospholipase and/or glycerophospholipid:cholesterol acyltransferase activities...
  62. You H, Lee J, Yoo Y, Kim J. A pathway involving protein kinase Cdelta up-regulates cytosolic phospholipase A(2)alpha in airway epithelium. Biochem Biophys Res Commun. 2004;321:657-64 pubmed
    ..Our results suggest that PKCdelta and ROS lie upstream of NF-kappaB, and we conclude that a PKCdelta-ROS-NF-kappaB cascade plays a pivotal role in cPLA(2)alpha induction by PMA. ..
  63. Dong B, Matsumura F. Roles of cytosolic phospholipase A2 and Src kinase in the early action of 2,3,7,8-tetrachlorodibenzo-p-dioxin through a nongenomic pathway in MCF10A cells. Mol Pharmacol. 2008;74:255-63 pubmed publisher immortalized, normal mammary epithelial cell line, TCDD rapidly activates the enzymatic activity of cytosolic phospholipase A2 (cPLA2) as at-tested to by arachidonic acid release within 15 min, followed by activation of Src kinase ..
  64. Müller C, Hardt M, Schwudke D, Neuman B, Pleschka S, Ziebuhr J. Inhibition of Cytosolic Phospholipase A2? Impairs an Early Step of Coronavirus Replication in Cell Culture. J Virol. 2018;92: pubmed publisher
    ..We obtained evidence to show that a cellular phospholipase, cPLA2?, which releases fatty acid from the sn-2 position of membrane-associated glycerophospholipids, is ..
  65. Yamaura S, Sakasegawa S, Koguma E, Ueda S, Kayamori Y, Sugimori D, et al. Novel enzymatic method for assaying Lp-PLA2 in serum. Clin Chim Acta. 2018;481:184-188 pubmed publisher
    ..The newly revealed substrate specificity of lysoplasmalogen-specific phospholipase D (lysophospholipase D (LysoPLD)) was exploited...
  66. Dennis E. Diversity of group types, regulation, and function of phospholipase A2. J Biol Chem. 1994;269:13057-60 pubmed
  67. Tashiro S, Sumi T, Uozumi N, Shimizu T, Nakamura T. B-Myb-dependent regulation of c-Myc expression by cytosolic phospholipase A2. J Biol Chem. 2004;279:17715-22 pubmed
    ..These findings provide new insights into the function of cPLA(2) in B-Myb-dependent gene expression. ..
  68. Pessach I, Shmelzer Z, Leto T, Dinauer M, Levy R. The C-terminal flavin domain of gp91phox bound to plasma membranes of granulocyte-like X-CGD PLB-985 cells is sufficient to anchor cytosolic oxidase components and support NADPH oxidase-associated diaphorase activity independent of cytosolic phosphol. J Leukoc Biol. 2006;80:630-9 pubmed
    ..Therefore, the assembled membrane-bound oxidase complex encompassing the flavin domain of gp91(phox) provides a docking site for cPLA(2) but is not the site of AA-based regulation of oxidase activity. ..
  69. Tian W, Wijewickrama G, Kim J, Das S, Tun M, Gokhale N, et al. Mechanism of regulation of group IVA phospholipase A2 activity by Ser727 phosphorylation. J Biol Chem. 2008;283:3960-71 pubmed
    ..Collectively, these studies provide new insight into the regulatory mechanism of cPLA(2)alpha through Ser(727) phosphorylation. ..
  70. Mathur A, Law M, Hamzehloei T, Megson I, Shaw D, Wei J. No association between the PPARG gene and schizophrenia in a British population. Prostaglandins Leukot Essent Fatty Acids. 2009;81:273-7 pubmed publisher
    ..To investigate a genetic link between these two diseases, the combined effects of the PLA2G4A, PTGS2 and PPARG genes were tested among 221 British nuclear families consisting of fathers, mothers and affected ..
  71. Coffey M, Coles B, Locke M, Bermudez Fajardo A, Williams P, Jarvis G, et al. Interactions of 12-lipoxygenase with phospholipase A2 isoforms following platelet activation through the glycoprotein VI collagen receptor. FEBS Lett. 2004;576:165-8 pubmed
    ..This study shows that platelet 12-H(P)ETE generation utilizes arachidonate substrate from both c- and sPLA2 and that 12-LOX functionally associates with both PLA2 isoforms. ..
  72. Leoncini G, Bruzzese D, Signorello M. Activation of p38 MAPKinase/cPLA2 pathway in homocysteine-treated platelets. J Thromb Haemost. 2006;4:209-16 pubmed
    ..Moreover, the incubation of platelets with HCy led to the phosphorylation of cytosolic phospholipase A2 (cPLA2). In addition HCy promoted cPLA2 activation, assessed as arachidonic acid release...
  73. Tang F, Chen Z, Ciszewski C, Setty M, Solus J, Tretiakova M, et al. Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15. J Exp Med. 2009;206:707-19 pubmed publisher
    ..These results reveal an unrecognized link between NKG2D and tissue inflammation, which may underlie the emerging role of NKG2D in various immunopathological conditions and define new therapeutic targets. ..
  74. Ghomashchi F, Naika G, Bollinger J, Aloulou A, Lehr M, Leslie C, et al. Interfacial kinetic and binding properties of mammalian group IVB phospholipase A2 (cPLA2beta) and comparison with the other cPLA2 isoforms. J Biol Chem. 2010;285:36100-11 pubmed publisher
    ..Human cPLA(2)? also displays Ca(2+)- and cardiolipin-enhanced interfacial binding and activity. The lysophospholipase, phospholipase A(1), and phospholipase A(2) activities of the full set of mammalian cPLA(2)s were quantified...
  75. Dessen A, Tang J, Schmidt H, Stahl M, Clark J, Seehra J, et al. Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism. Cell. 1999;97:349-60 pubmed
    b>Cytosolic phospholipase A2 initiates the biosynthesis of prostaglandins, leukotrienes, and platelet-activating factor (PAF), mediators of the pathophysiology of asthma and arthritis...
  76. Mavoungou E, Georges Courbot M, Poaty Mavoungou V, Nguyen H, Yaba P, Delicat A, et al. HIV and SIV envelope glycoproteins induce phospholipase A2 activation in human and macaque lymphocytes. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;16:1-9 pubmed
    ..However, this effect is not sufficient to accomplish fusion. These data indicate that the specific step of fusion may be downstream from PLA2 activation. ..
  77. Perisic O, Fong S, Lynch D, Bycroft M, Williams R. Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2. J Biol Chem. 1998;273:1596-604 pubmed
    b>Cytosolic phospholipase A2 (cPLA2) is a calcium-sensitive 85-kDa enzyme that hydrolyzes arachidonic acid-containing membrane phospholipids to initiate the biosynthesis of eicosanoids and platelet-activating factor, potent inflammatory ..
  78. Wang H, Wen Y, Mooney S, Behr B, Polan M. Phospholipase A(2) and cyclooxygenase gene expression in human preimplantation embryos. J Clin Endocrinol Metab. 2002;87:2629-34 pubmed
    ..COX-1 and COX-2 are differentially expressed, with COX-2 being primarily expressed by trophectoderm in late-stage human preimplantation embryos, which may promote embryonic differentiation and implantation. ..
  79. Malmberg N, Van Buskirk D, Falke J. Membrane-docking loops of the cPLA2 C2 domain: detailed structural analysis of the protein-membrane interface via site-directed spin-labeling. Biochemistry. 2003;42:13227-40 pubmed
  80. Wei J, Hemmings G. A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in schizophrenia. Prostaglandins Leukot Essent Fatty Acids. 2005;73:441-5 pubmed
    ..the combined effect of the CLDN5 gene and those for the phospholipid metabolism pathway, including PTGS1, PTGS2, PLA2G4A and PLA2G4C...
  81. Casas J, Gijón M, Vigo A, Crespo M, Balsinde J, Balboa M. Overexpression of cytosolic group IVA phospholipase A2 protects cells from Ca2+-dependent death. J Biol Chem. 2006;281:6106-16 pubmed
    ..These results suggest that early cell death events promoted by an overload of calcium can be prevented by the presence of high levels of arachidonic acid. ..
  82. Xu L, Han C, Lim K, Wu T. Cross-talk between peroxisome proliferator-activated receptor delta and cytosolic phospholipase A(2)alpha/cyclooxygenase-2/prostaglandin E(2) signaling pathways in human hepatocellular carcinoma cells. Cancer Res. 2006;66:11859-68 pubmed
    ..Thus, PPARdelta induces COX-2 expression and the COX-2-derived PGE(2) further activates PPARdelta via cPLA(2)alpha. Such an interaction forms a novel feed-forward growth-promoting signaling that may play a role in hepatocarcinogenesis. ..
  83. Barbosa N, Junqueira R, Vallada H, Gattaz W. Association between BanI genotype and increased phospholipase A2 activity in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2007;257:340-3 pubmed
    ..004 for both). Our data suggest an association between BanI genotype and PLA2G4A activity in platelets and that the presence of the allele A2 may increase risk for schizophrenia through an ..
  84. Shimizu M, Nakamura H, Hirabayashi T, Suganami A, Tamura Y, Murayama T. Ser515 phosphorylation-independent regulation of cytosolic phospholipase A2alpha (cPLA2alpha) by calmodulin-dependent protein kinase: possible interaction with catalytic domain A of cPLA2alpha. Cell Signal. 2008;20:815-24 pubmed publisher
    ..Our findings show a possible effect of CaM kinase on cPLA(2)alpha in a catalytic domain A-dependent and Ser515-independent manner. ..
  85. Nadalin S, Rubesa G, Giacometti J, VULIN M, Tomljanović D, Vraneković J, et al. BanI polymorphism of cytosolic phospholipase A2 gene is associated with age at onset in male patients with schizophrenia and schizoaffective disorder. Prostaglandins Leukot Essent Fatty Acids. 2008;78:351-60 pubmed publisher
    ..We investigated allelic and genotype frequencies of PLA2G4A BanI polymorphism and the rs4375 in PLA2G6A in Croatian schizophrenic patients (n=81) and controls (n=182), using ..
  86. Yazlovitskaya E, Linkous A, Thotala D, Cuneo K, Hallahan D. Cytosolic phospholipase A2 regulates viability of irradiated vascular endothelium. Cell Death Differ. 2008;15:1641-53 pubmed publisher
    ..In summary, an immediate radiation-induced cPLA(2)-dependent signaling was identified that regulates cell viability and, therefore, represents one of the key regulators of radioresistance of vascular endothelial cells. ..
  87. Shmelzer Z, Karter M, Eisenstein M, Leto T, Hadad N, Ben Menahem D, et al. Cytosolic phospholipase A2alpha is targeted to the p47phox-PX domain of the assembled NADPH oxidase via a novel binding site in its C2 domain. J Biol Chem. 2008;283:31898-908 pubmed publisher
    We have previously demonstrated a physical interaction between cytosolic phospholipase A2alpha (cPLA2) and the assembled NADPH oxidase on plasma membranes following neutrophil stimulation...
  88. Zhang Q, Wang D, Singh N, Kundumani Sridharan V, Gadiparthi L, Rao C, et al. Activation of cytosolic phospholipase A2 downstream of the Src-phospholipase D1 (PLD1)-protein kinase C ? (PKC?) signaling axis is required for hypoxia-induced pathological retinal angiogenesis. J Biol Chem. 2011;286:22489-98 pubmed publisher
    ..These observations suggest that cPLA(2)-dependent AA release is required for VEGF-induced Src-PLD1-PKC?-mediated pathological retinal angiogenesis. ..
  89. Gentile M, Reccia M, Sorrentino P, Vitale E, Sorrentino G, Puca A, et al. Role of cytosolic calcium-dependent phospholipase A2 in Alzheimer's disease pathogenesis. Mol Neurobiol. 2012;45:596-604 pubmed publisher
    ..Findings obtained from in vitro studies, animal models, and human brain imaging analysis point towards cPLA2 as a key molecule in the onset and maintenance of the neurodegenerative mechanism(s) of AD...
  90. Zulueta A, Razzari C, Fontana G, Femia E, Faioni E, Cattaneo M, et al. Instability of cytosolic phospholipase A2? variant upon cellular expression as a basis for its clinical presentation. Thromb Haemost. 2015;114:208-10 pubmed publisher
  91. Fu H, He Y, Qi L, Chen L, Luo Y, Chen L, et al. cPLA2α activates PI3K/AKT and inhibits Smad2/3 during epithelial-mesenchymal transition of hepatocellular carcinoma cells. Cancer Lett. 2017;403:260-270 pubmed publisher
    b>Cytosolic phospholipase A2α (cPLA2α), a key phospholipase that regulates lipid metabolism, plays an important role in tumor progression...
  92. Lang C, Hiller M, Flieger A. Disulfide loop cleavage of Legionella pneumophila PlaA boosts lysophospholipase A activity. Sci Rep. 2017;7:16313 pubmed publisher
    ..PlaA is a lysophospholipase A (LPLA) that destabilizes the phagosomal membrane in absence of a protective factor...