Affinage

PLA2G4A

Cytosolic phospholipase A2 · UniProt P47712

Round 2 corrected
Length
749 aa
Mass
85.2 kDa
Annotated
2026-04-28
65 papers in source corpus 24 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLA2G4A (cPLA2α) is an 85-kDa cytosolic phospholipase A2 that selectively cleaves arachidonic acid from membrane phospholipids via a Ser-Asp catalytic dyad housed in a deep hydrophobic funnel, thereby initiating eicosanoid biosynthesis including prostaglandin E2 and platelet-activating factor (PMID:1904318, PMID:10319815, PMID:15475363). Its N-terminal C2 domain mediates calcium-dependent translocation to Golgi, ER, and perinuclear membranes, with differential targeting governed by intracellular calcium concentration, and co-localization with COX-1 at the trans-Golgi couples arachidonate release to prostaglandin synthesis (PMID:11375391, PMID:12711701). Full activation requires convergent phosphorylation by ERK/MAP kinase at Ser-505 and by MNK1 at Ser-727 in addition to calcium elevation (PMID:8381049, PMID:10978317). Beyond classical eicosanoid production, PLA2G4A controls lysosomal membrane integrity—its activation causes lysosomal membrane permeabilization and autophagy impairment in neurons—and remodels membrane phospholipid composition to regulate ferroptosis susceptibility in cancer cells (PMID:31238788, PMID:41400081).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1991 High

    Identification of cPLA2 as a cloned 85-kDa enzyme with arachidonate selectivity and a PKC-homologous C2 domain established the molecular identity and calcium-dependent membrane-binding mechanism of the enzyme.

    Evidence cDNA cloning, bacterial/mammalian expression, in vitro phospholipid hydrolysis and calcium-dependent membrane translocation assays

    PMID:1869522 PMID:1904318

    Open questions at the time
    • Catalytic mechanism and active-site residues not yet defined
    • In vivo physiological roles unknown
    • Regulatory phosphorylation not characterized
  2. 1993 High

    Demonstration that MAP kinase phosphorylates Ser-505 and that this modification is required for agonist-stimulated arachidonate release established the first direct regulatory link between MAPK signaling and cPLA2 activation.

    Evidence In vitro MAP kinase assay, Ser505Ala mutagenesis, intact cell arachidonate release

    PMID:8381049

    Open questions at the time
    • Additional phosphorylation sites not yet mapped
    • Upstream kinase pathways beyond ERK not explored
    • Relationship between phosphorylation and membrane translocation unclear
  3. 1996 High

    Mapping of four in vivo phosphorylation sites (Ser-437, -454, -505, -727) and identification of p38 MAPK as an additional kinase revealed a multisite phosphorylation code, while showing that p38-dependent phosphorylation alone is insufficient for activation.

    Evidence 32P-labeling, mass spectrometry, p38 inhibitors in human monocytes and platelets

    PMID:8636128 PMID:8910365

    Open questions at the time
    • Identity of the kinase for Ser-727 unknown
    • Combinatorial effects of multiple phosphorylation events untested
    • Structural basis for phosphorylation-dependent activation unclear
  4. 1998 High

    Crystal structures of the C2 domain (2.4 Å) and then full-length cPLA2 (2.5 Å) revealed the calcium-binding architecture, membrane-insertion geometry, and a novel Ser-Asp catalytic dyad in a hydrophobic funnel that explains arachidonate selectivity.

    Evidence X-ray crystallography at 2.4 Å (C2 domain) and 2.5 Å (full-length), later confirmed by X-ray reflectivity of C2 on lipid monolayers

    PMID:10319815 PMID:15994899 PMID:9430701

    Open questions at the time
    • No structure of enzyme–membrane or enzyme–substrate complex
    • Lid dynamics during catalysis not resolved
    • Structural impact of phosphorylation not determined
  5. 2000 High

    Identification of MNK1 as the Ser-727 kinase downstream of p38 completed the two-site phosphorylation model: full cPLA2 activation requires both Ser-505 (ERK) and Ser-727 (MNK1) phosphorylation together with calcium.

    Evidence In vitro kinase assay with MNK1, mass spectrometry, dominant-negative MNK1, phosphorylation-site mutants, arachidonate release

    PMID:10978317

    Open questions at the time
    • Relative quantitative contribution of each phosphorylation event not determined
    • Whether other kinases target Ser-727 in specific cell types unknown
  6. 2001 High

    Live-cell imaging showed that cPLA2 targets the Golgi at low calcium and extends to ER/perinuclear membranes at higher calcium, with specific co-localization with COX-1 at the trans-Golgi, establishing how spatial coupling between cPLA2 and cyclooxygenases governs prostaglandin synthesis.

    Evidence EGFP-cPLA2 live-cell imaging, calcium quantitation, organelle markers, brefeldin A treatment in A549 and CHO cells

    PMID:11375391 PMID:12711701

    Open questions at the time
    • Whether cPLA2 functionally couples to COX-2 at a distinct compartment not resolved
    • Mechanism of preferential Golgi targeting at low calcium not defined
  7. 2004 High

    Knockout and inhibitor studies in neutrophils established that cPLA2α is essential for arachidonate release, PAF biosynthesis, and bacterial killing in innate immunity, while dispensable for NADPH oxidase activation and phagocytosis.

    Evidence cPLA2α knockout mice, Pyrrolidine-1 inhibitor, AA/PAF assays, bacterial killing assay, intratracheal E. coli infection

    PMID:15475363

    Open questions at the time
    • Specific eicosanoid species mediating bactericidal activity not identified
    • Whether adaptive immune functions also depend on cPLA2α unclear
  8. 2019 High

    Discovery that cPLA2α activation causes lysosomal membrane permeabilization (LMP), impairs autophagy flux, and promotes neuronal death after traumatic brain injury revealed a non-eicosanoid effector arm of cPLA2α in neurodegeneration.

    Evidence Mouse TBI model, LC-MS/MS lysosomal lipidomics, pharmacological PLA2G4A inhibition (AACOCF3), autophagy flux assays, amyloid-β in vitro

    PMID:31238788

    Open questions at the time
    • Specific lysosomal lipid species mediating LMP not identified
    • Whether LMP role is cell-type specific beyond neurons unknown
    • Relationship between LMP and eicosanoid production not dissected
  9. 2022 Medium

    Multiple studies converged on PLA2G4A as a regulator of ferroptosis susceptibility: PTRF stabilizes PLA2G4A protein to promote ferroptosis in ischemic neurons, while ATF6α-driven PLA2G4A/PGE2 production confers ferroptosis resistance in prostate cancer, and NRF2–PIR transcriptional activation of PLA2G4A remodels membranes to deplete PUFA-phospholipids in CRC.

    Evidence Co-IP (PTRF–PLA2G4A), ChIP (ATF6α and NRF2/PIR at PLA2G4A promoter), lipidomics, ferroptosis assays, in vivo ischemia and tumorigenesis models

    PMID:35089606 PMID:35547748 PMID:41400081

    Open questions at the time
    • Context-dependent pro- versus anti-ferroptotic role not mechanistically reconciled
    • Specific PUFA-PE species remodeled by PLA2G4A not fully catalogued
    • Whether ferroptosis regulation is independent of canonical eicosanoid pathways unclear
  10. 2025 Medium

    PLA2G4A was shown to physically interact with CENPF and to participate in GSK3β/NF-κB-regulated lysosomal integrity in Alzheimer's models, expanding its interactome and reinforcing its role in lysosomal biology.

    Evidence Co-IP of CENPF–PLA2G4A in glioma cells; GSK3β-isoform-specific knockdown in APP/PS1 mice with lysosomal integrity assays

    PMID:40025532 PMID:42047940

    Open questions at the time
    • Direct binding interface between CENPF and PLA2G4A not mapped
    • Functional significance of CENPF interaction for catalytic activity unknown
    • Whether GSK3β regulation of PLA2G4A is NF-κB-exclusive or involves additional pathways not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Outstanding questions include: how phosphorylation at multiple sites structurally alters the catalytic domain and lid dynamics; what determines whether PLA2G4A activity is pro- or anti-ferroptotic in different cellular contexts; and whether its transacylase activity toward phosphatidylglycerol (BMP production) represents a physiologically significant catalytic mode distinct from sn-2 hydrolysis.
  • No structure of phosphorylated cPLA2α or enzyme–membrane complex
  • Pro- vs. anti-ferroptotic context dependence mechanistically unresolved
  • Transacylase activity awaits independent confirmation beyond preprint

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0016787 hydrolase activity 4
Localization
GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2
Partners
CENPFGSK3BMAPK1MKNK1PTGS1PTRF

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 PLA2G4A (cPLA2) was cloned as an 85-kDa cytosolic phospholipase A2 that selectively cleaves arachidonic acid from membrane phospholipids and contains an N-terminal C2 domain homologous to PKC that mediates calcium-dependent translocation to membrane vesicles. cDNA cloning, bacterial and hamster cell expression, in vitro phospholipid hydrolysis assay, calcium-dependent membrane translocation assay Cell High 1869522 1904318
1993 cPLA2 (PLA2G4A) is phosphorylated and activated by MAP kinase at Ser-505; phosphorylation of this site increases enzymatic activity and is required for agonist-stimulated arachidonate release from intact cells. In vitro kinase assay with MAP kinase, site-directed mutagenesis (Ser-505→Ala), intact cell arachidonate release assay Cell High 8381049
1996 Human cPLA2 is phosphorylated in vivo at Ser-437, Ser-454, Ser-505, and Ser-727; phosphorylation at Ser-727 is most strongly induced by okadaic acid and correlates with arachidonic acid release in human monocytes. 32P-labeling, HPLC of tryptic digests, mass spectrometry, Edman sequencing of recombinant cPLA2 in Sf9 cells and human monocytes The Journal of biological chemistry High 8636128
1996 p38 mitogen-activated protein kinase phosphorylates cPLA2 (PLA2G4A) on proline-directed sites in thrombin-stimulated platelets; however, blocking proline-directed phosphorylation does not prevent arachidonic acid release, indicating p38-independent activation mechanisms also exist. p38 kinase inhibitors, immunoprecipitation, phosphorylation assays, arachidonic acid release assay in human platelets The Journal of biological chemistry High 8910365
1998 The 2.4 Å crystal structure of the cPLA2 C2 domain reveals a beta-sandwich with two calcium-binding sites; hydrophobic residues flanked by a basic strip constitute the membrane-binding motif, with hydrophobic interactions predominating over electrostatic forces for membrane binding. X-ray crystallography at 2.4 Å, multiple isomorphous replacement The Journal of biological chemistry High 9430701
1999 The 2.5 Å crystal structure of full-length human cPLA2 reveals an N-terminal C2 domain and a catalytic unit with novel topology; an unusual Ser-Asp catalytic dyad in a deep hydrophobic funnel selectively cleaves arachidonyl phospholipids, and a flexible lid must move to allow substrate access. X-ray crystallography at 2.5 Å Cell High 10319815
1999 Two paralogs of cPLA2alpha were identified (cPLA2beta and cPLA2gamma); mutagenesis confirmed that the catalytic residues of cPLA2alpha (including Arg-566) are conserved and essential for activity in all three enzymes, while cPLA2gamma lacks the C2 domain and is calcium-independent. cDNA cloning, site-directed mutagenesis of catalytic residues, in vitro phospholipase activity assay, calcium dependence assay The Journal of biological chemistry High 10085124
2000 cPLA2 is phosphorylated at Ser-727 by MNK1 (and PRAK1) in a p38-dependent pathway; phosphorylation at both Ser-505 and Ser-727 together with elevated Ca2+ is required for full agonist-stimulated activation; dominant-negative MNK1 significantly inhibits cPLA2-mediated arachidonate release. In vitro kinase assay with MNK1/MSK1/PRAK1, mass spectrometry for site identification, stable transfection of phosphorylation-site mutants, dominant-negative MNK1 expression, arachidonate release assay The Journal of biological chemistry High 10978317
2001 cPLA2 translocates to the Golgi at low sustained Ca2+ (~100–125 nM), and to Golgi, ER, and perinuclear membranes at higher Ca2+ (~210–280 nM); the C2 domain governs differential Ca2+-dependent membrane targeting while the catalytic domain regulates translocation rate and enzyme residence; arachidonic acid release is proportional to extent of translocation. EGFP-fusion live-cell imaging, Ca2+ imaging, agonist stimulation, organelle markers, deletion constructs (EGFP-C2 vs. EGFP-FL) The Journal of biological chemistry High 11375391
2003 cPLA2-alpha (PLA2G4A) relocates from the cytosol/nucleus to the trans-Golgi stack and trans-Golgi network following Ca2+ elevation in A549 lung epithelial cells; it co-localizes specifically with COX-1 but not COX-2 at the Golgi, suggesting a role in Golgi membrane trafficking and prostaglandin synthesis. Confocal microscopy, Ca2+ ionophore stimulation, double immunofluorescence with Golgi subcompartment markers, brefeldin A treatment Journal of cell science High 12711701
2003 In murine mesangial cells, secretory PLA2s (groups IIa and V) regulate the activity of cPLA2alpha (PLA2G4A), which is the enzyme directly responsible for H2O2-induced arachidonic acid release; this cross-talk requires PKC and ERK1/2 signaling but not constitutive ERK activation alone. Recombinant adenovirus-mediated expression of PLA2 isoforms in cPLA2alpha-null cells, AA release assay, MEK-1 inhibitor (U0126), PKC inhibitor (GF1092030x), intracellular Ca2+ chelation The Journal of biological chemistry High 12676927
2004 cPLA2alpha (PLA2G4A) is required for neutrophil arachidonate release and platelet-activating factor (PAF) biosynthesis but not for NADPH oxidase activation or phagocytosis; it is necessary for efficient bacterial killing in vitro (partially rescued by exogenous arachidonic acid or PAF) and for pulmonary innate immune responses in vivo. Pharmacological inhibition (Pyrrolidine-1), cPLA2alpha gene knockout mice, AA release assay, PAF ELISA, NADPH oxidase assay, bacterial killing assay, intratracheal E. coli infection model The Journal of biological chemistry High 15475363
2005 The cPLA2alpha-C2 domain binds to SOPC phospholipid monolayers in a Ca2+-dependent manner; the Ca2+-binding loops CBL1 and CBL3 penetrate 2 Å into the lipid tailgroup region with Ca2+ ions positioned within 1 Å of the lipid phosphate group; hydrophobic residues in these loops are critical for membrane binding. X-ray reflectivity of Langmuir monolayers, C2 domain mutants, Ca2+-free controls Biophysical journal High 15994899
2006 cPLA2alpha (PLA2G4A) is not required for proton channel activation or NADPH oxidase respiratory burst in human eosinophils or murine granulocytes; PKC (not cPLA2alpha) is the essential upstream regulator of proton channel gating, refuting the prevailing arachidonic acid-cPLA2alpha model. cPLA2alpha-specific inhibitors (Wyeth-1, pyrrolidine-2, AACOCF3), cPLA2alpha gene knockout mice, PKC inhibitors, perforated-patch electrophysiology, electron current measurement The Journal of physiology High 17185330
2006 PLA2G4A expression in bovine granulosa cells is upregulated up to 45-fold by hCG/LH at ovulation via the adenylyl cyclase/cAMP pathway (forskolin mimics), with protein induction starting at 18 h post-hCG and peaking at 24 h; PLA2G4A localizes primarily to mural granulosa cells. cDNA characterization, quantitative RT-PCR across follicular stages, immunoblot, immunohistochemistry, forskolin stimulation in vitro Biology of reproduction Medium 16510840
2019 PLA2G4A activation causes lysosomal membrane permeabilization (LMP) in neurons, leading to inhibition of autophagy flux and neuronal cell death following traumatic brain injury; pharmacological inhibition of PLA2G4A in vivo attenuates TBI-induced LMP, restores autophagy, reduces neuronal loss, and improves neurological outcomes; PLA2G4A also mediates amyloid-β-induced LMP in vitro. Controlled cortical impact TBI mouse model, LC-MS/MS lysosomal lipid profiling, pharmacological PLA2G4A inhibition (AACOCF3), cell line and primary neuron experiments, autophagy flux assays (LC3, SQSTM1), cathepsin release, immunofluorescence Autophagy High 31238788
2019 ANXA10 promotes cholangiocarcinoma EMT and metastasis by upregulating PLA2G4A expression, which in turn increases PGE2 production and activates STAT3 signaling; the ANXA10/PLA2G4A/PGE2/STAT3 axis drives tumor progression in extrahepatic CCA. mRNA sequencing, in vitro cell invasion/migration assays, in vivo orthotopic model, ELISA for PGE2, Western blot for STAT3 activation, knockdown/overexpression EBioMedicine Medium 31492557
2022 PTRF overexpression in neurons after ischemia-reperfusion injury enhances PLA2G4A activity and stability by decreasing its proteasome-mediated degradation; PTRF is transcriptionally regulated by HIF-1α and STAT3 binding to its promoter; the PTRF/PLA2G4A axis drives lipid peroxidation, autophagy, and ferroptosis in neurons. ChIP, luciferase assay, co-IP, lentiviral-sgRNA knockdown, AAV-shRNA in primary neurons and mice, Western blot for proteasome pathway components, infarct volume measurement Theranostics Medium 35547748
2022 ATF6α transcriptionally activates PLA2G4A (ChIP confirmed); PLA2G4A-mediated AA release and subsequent PGE2 production acts as an antiferroptotic factor, conferring ferroptosis resistance in prostate cancer cells; inhibition of ATF6α or PLA2G4A promotes ferroptotic cell death. ChIP, AA and PGE2 ELISA, Western blot, gene knockdown/overexpression, MTS/BrdU proliferation assays, cell death assay The Prostate Medium 35089606
2021 PLA2G4A overexpression in colorectal cancer cells induces CD39+γδ Treg polarization via the PLA2G4A/arachidonic acid metabolic pathway, suppressing antitumor immune response; quantitative mass spectrometry linked CD39+γδ Treg polarization to abnormal PLA2G4A activation in right-sided CRC. Quantitative mass spectrometry, in vitro co-culture system, orthotopic murine CRC model, flow cytometry for Treg phenotyping, Pla2g4a overexpression in CT26 cells JCI insight Medium 34283812
2025 CENPF physically interacts with PLA2G4A (co-IP confirmed) in glioma cells, promoting downstream mTORC1 and NF-κB signaling; combined silencing of CENPF and pharmacological inhibition of PLA2G4A (AACOCF3) induces glioma cell apoptosis synergistically. Molecular docking, co-immunoprecipitation, GSEA, CCK-8, Transwell, flow cytometry, Western blot for mTORC1/NF-κB Cancer cell international Medium 40025532
2025 PIR (Pirin) transcriptionally activates PLA2G4A via an NRF2-PIR axis triggered by ferroptosis; PLA2G4A promotes MUFA/SFA species and depletes PUFA-phospholipids to create a ferroptosis-resistant membrane lipidome; restoration of PLA2G4A rescues ferroptosis resistance in PIR-deficient CRC cells. NRF2 ChIP at PIR promoter, lipidomics, PLA2G4A knockdown/overexpression, AACOCF3 inhibition, AOM/DSS tumorigenesis model, in vitro ferroptosis assays Advanced science Medium 41400081
2026 GSK3β suppression by AS1842856 reduces NF-κB-mediated PLA2G4A expression; decreased PLA2G4A restores lysosomal membrane integrity and enhances lysosomal degradation of Aβ in APP/PS1 mice; GSK3β (not GSK3α) knockdown reproduces the suppressive effect on PLA2G4A. APP/PS1 mouse model, N2a-sw cells, Western blot, siRNA knockdown of GSK3α/β, lysosomal integrity assays, Aβ burden quantification, NF-κB pathway analysis CNS neuroscience & therapeutics Medium 42047940
2025 PACERR lncRNA interacts with an enhancer element of cPLA2 (PLA2G4A) in cis, affecting its transcriptional activation, and escorts cPLA2 protein to the nuclear membrane where it releases arachidonic acid to further activate COX-2 in response to HDL. ASO silencing of PACERR, cPLA2 localization and activity assays, enhancer interaction (preprint mechanistic study) bioRxivpreprint Low
2024 Members of the cytosolic PLA2 group IV (PLA2G4) family, including PLA2G4A, catalyze transacylation of phosphatidylglycerol (PG) to produce acyl-PG, a precursor of the lysosomal lipid BMP; overexpression of PLA2G4A was sufficient to correct BMP deficiency in CLN5-knockout HEK293 cells. Overexpression in HEK293 cells, lipidomics, CLN5 knockout rescue experiment bioRxivpreprint Low

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
1993 cPLA2 is phosphorylated and activated by MAP kinase. Cell 1729 8381049
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
1991 A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. Cell 1647 1904318
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
1994 Diversity of group types, regulation, and function of phospholipase A2. The Journal of biological chemistry 1216 8175726
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2008 Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nature genetics 817 18583979
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1991 Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2. The Journal of biological chemistry 436 1869522
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1996 p38 mitogen-activated protein kinase phosphorylates cytosolic phospholipase A2 (cPLA2) in thrombin-stimulated platelets. Evidence that proline-directed phosphorylation is not required for mobilization of arachidonic acid by cPLA2. The Journal of biological chemistry 414 8910365
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1999 Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism. Cell 294 10319815
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
1998 Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2. The Journal of biological chemistry 231 9430701
2010 Poor replication of candidate genes for major depressive disorder using genome-wide association data. Molecular psychiatry 220 20351714
2001 Intracellular calcium signals regulating cytosolic phospholipase A2 translocation to internal membranes. The Journal of biological chemistry 205 11375391
2000 Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases. The Journal of biological chemistry 202 10978317
2004 Regulatory mechanism and physiological role of cytosolic phospholipase A2. Biological & pharmaceutical bulletin 176 15305015
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
1999 Molecular cloning of two new human paralogs of 85-kDa cytosolic phospholipase A2. The Journal of biological chemistry 165 10085124
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
1996 Identification of phosphorylation sites of human 85-kDa cytosolic phospholipase A2 expressed in insect cells and present in human monocytes. The Journal of biological chemistry 151 8636128
2020 Updating Phospholipase A2 Biology. Biomolecules 148 33086624
2006 The DNA sequence and biological annotation of human chromosome 1. Nature 144 16710414
2019 PLA2G4A/cPLA2-mediated lysosomal membrane damage leads to inhibition of autophagy and neurodegeneration after brain trauma. Autophagy 142 31238788
2017 Long non-coding RNA SNHG14 promotes microglia activation by regulating miR-145-5p/PLA2G4A in cerebral infarction. Neuroscience 121 28215748
2003 Cross-talk between cytosolic phospholipase A2 alpha (cPLA2 alpha) and secretory phospholipase A2 (sPLA2) in hydrogen peroxide-induced arachidonic acid release in murine mesangial cells: sPLA2 regulates cPLA2 alpha activity that is responsible for arachidonic acid release. The Journal of biological chemistry 121 12676927
2004 Cytosolic phospholipase A2-alpha is necessary for platelet-activating factor biosynthesis, efficient neutrophil-mediated bacterial killing, and the innate immune response to pulmonary infection: cPLA2-alpha does not regulate neutrophil NADPH oxidase activity. The Journal of biological chemistry 83 15475363
2022 Neuronal STAT3/HIF-1α/PTRF axis-mediated bioenergetic disturbance exacerbates cerebral ischemia-reperfusion injury via PLA2G4A. Theranostics 82 35547748
2019 Annexin10 promotes extrahepatic cholangiocarcinoma metastasis by facilitating EMT via PLA2G4A/PGE2/STAT3 pathway. EBioMedicine 69 31492557
2006 Sustained activation of proton channels and NADPH oxidase in human eosinophils and murine granulocytes requires PKC but not cPLA2 alpha activity. The Journal of physiology 63 17185330
2022 ATF6α promotes prostate cancer progression by enhancing PLA2G4A-mediated arachidonic acid metabolism and protecting tumor cells against ferroptosis. The Prostate 53 35089606
2005 X-ray reflectivity studies of cPLA2{alpha}-C2 domains adsorbed onto Langmuir monolayers of SOPC. Biophysical journal 44 15994899
2021 PLA2G4A promotes right-sided colorectal cancer progression by inducing CD39+γδ Treg polarization. JCI insight 40 34283812
2004 A study of a genetic association between the PTGS2/PLA2G4A locus and schizophrenia. Prostaglandins, leukotrienes, and essential fatty acids 35 15041036
2006 Expression of phospholipase A2 group IVA (PLA2G4A) is upregulated by human chorionic gonadotropin in bovine granulosa cells of ovulatory follicles. Biology of reproduction 33 16510840
2003 Association of cPLA2-alpha and COX-1 with the Golgi apparatus of A549 human lung epithelial cells. Journal of cell science 31 12711701
2020 LncRNA NEAT1 regulates chondrocyte proliferation and apoptosis via targeting miR-543/PLA2G4A axis. Human cell 26 33040229
2012 HERV-E-mediated modulation of PLA2G4A transcription in urothelial carcinoma. PloS one 26 23145155
2010 Effect of Ga-Al-As laser irradiation on COX-2 and cPLA2-alpha expression in compressed human periodontal ligament cells. Lasers in surgery and medicine 20 20662025
2018 Inhibition of PLA2G4A Reduces the Expression of Lung Cancer-Related Cytokines. DNA and cell biology 19 30328712
2012 The impact of PLA2G4A and PTGS2 gene polymorphisms, and red blood cell PUFAs deficit on niacin skin flush response in schizophrenia patients. Prostaglandins, leukotrienes, and essential fatty acids 19 23219238
2024 PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer. Journal of translational medicine 15 38454407
2012 Association of PLA2G4A with myocardial infarction is modulated by dietary PUFAs. The American journal of clinical nutrition 15 22378731
2021 Acupuncture therapy protects PCOS patients with diabetes by regulating miR-32-3p/PLA2G4A pathway. American journal of translational research 14 34539997
2003 Association of a F479L variant in the cytosolic phospholipase A2 gene (PLA2G4A) with decreased glucose turnover and oxidation rates in Pima Indians. Molecular genetics and metabolism 14 12765847
2015 Association study of genetic variants in PLA2G4A, PLCG1, LAT, SYK, and TNFRS11A genes in NSAIDs-induced urticaria and/or angioedema patients. Pharmacogenetics and genomics 12 26398624
2021 Nuclear progesterone receptor regulates ptger4b and PLA2G4A expression in zebrafish (Danio rerio) ovulation. General and comparative endocrinology 10 34252451
2025 Xingxiao pills suppresses lung adenocarcinoma progression by modulating lipid metabolism and inhibiting the PLA2G4A-GLI1-SOX2 Axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 8 40339555
2023 Lnc-PLA2G4A-4 facilitates the progression of hepatocellular carcinoma by inducing versican expression via sponging miR-23b-3p. Heliyon 5 37554815
2018 An association between the BanI polymorphism of the PLA2G4A gene for calcium-dependent phospholipase A2 and plasma glucose levels among females with schizophrenia. Prostaglandins, leukotrienes, and essential fatty acids 5 30103930
2025 CENPF interaction with PLA2G4A promotes glioma growth by modulating mTORC1 and NF-κB pathways. Cancer cell international 4 40025532
2012 PLA2G4A mutants modified protective effect of tea consumption against colorectal cancer. International journal of colorectal disease 2 22358383
2024 Copy number deletion of PLA2G4A affects the susceptibility and clinical phenotypes of schizophrenia. Schizophrenia (Heidelberg, Germany) 1 38816399
2026 A perspective: PLA2G4A as drug target for vascular inflammation in Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association 0 41950067
2026 AS1842856 Reduces β-Amyloid Burden via Inhibiting PLA2G4A-Mediated Lysosomal Dysfunction in APP/PS1 Mice. CNS neuroscience & therapeutics 0 42047940
2025 Pirin Transcriptionally Regulates PLA2G4A To Inhibit Ferroptosis in Colorectal Cancer via Lipid Profile Remodeling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41400081
2024 Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers: A case report and review of literature. World journal of gastrointestinal surgery 0 38577076
2007 Expression Analysis of cPLA2 Alpha Interacting TIP60 in Diabetic KKAy and Non-Diabetic C57BL Wild-Type Mice: No Impact of Transient and Stable TIP60 Overexpression on Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells. The review of diabetic studies : RDS 0 18084672