PLA2G4A Antibody

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Product Specs

Buffer
The antibody is provided as a liquid solution in PBS containing 50% glycerol, 0.5% BSA, and 0.02% sodium azide.
Form
Liquid
Lead Time
Typically, we can ship the products within 1-3 business days after receiving your order. Delivery time may vary depending on the purchasing method or location. For specific delivery timelines, please contact your local distributor.
Synonyms
Calcium dependent phospholipid binding protein antibody; CPLA 2 antibody; cPLA2 alpha antibody; cPLA2 antibody; Cytosolic phospholipase A2 antibody; Cytosolic phospholipase A2 group IVA antibody; Lysophospholipase antibody; MGC126350 antibody; PA24A_HUMAN antibody; Phosphatidylcholine 2 acylhydrolase antibody; Phosphatidylcholine 2-acylhydrolase antibody; Phospholipase A2 group 4 A antibody; Phospholipase A2 group IVA (cytosolic calcium dependent) antibody; Phospholipase A2 group IVA antibody; PhospholipaseA2 antibody; PLA2G4 antibody; pla2g4a antibody
Target Names
Uniprot No.

Target Background

Function
PLA2G4A, also known as cytosolic phospholipase A2 alpha (cPLA2α), is an enzyme that plays a crucial role in the regulation of cellular lipid metabolism and signaling. It exhibits primarily calcium-dependent phospholipase and lysophospholipase activities, which are essential for membrane lipid remodeling and biosynthesis of lipid mediators involved in the inflammatory response. cPLA2α plays a significant role in various physiological processes, including embryo implantation and parturition, by initiating prostanoid production. This enzyme preferentially hydrolyzes the ester bond of the fatty acyl group attached to the sn-2 position of phospholipids (phospholipase A2 activity). It selectively hydrolyzes the sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis through the cyclooxygenase pathway. In an alternative eicosanoid biosynthesis pathway, cPLA2α hydrolyzes the sn-2 fatty acyl chain of eicosanoid lysophospholipids to release free bioactive eicosanoids. Additionally, cPLA2α can hydrolyze the ester bond of the fatty acyl group attached to the sn-1 position of phospholipids (phospholipase A1 activity) when an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific. cPLA2α possesses calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides. It also exhibits O-acyltransferase activity, catalyzing the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis.
Gene References Into Functions

PLA2G4A - Gene References

  1. PLA2G4A up-regulated the protein expression of E-cadherin and down-regulated the protein expression of vimentin, inhibiting ESCC cell mobility and invasiveness. PMID: 30071514
  2. The impaired phospholipid level and remarkable increase in cPLA2 concentration suggested their roles in the etiology of autism. PMID: 28724385
  3. cPLA2alpha, which releases fatty acid from the sn-2 position of membrane-associated glycerophospholipids, is critically involved in coronavirus replication, likely by producing lysophospholipids necessary for forming the specialized membrane compartments where viral RNA synthesis takes place. PMID: 29167338
  4. Research indicated that IFN-gamma induces autophagy-associated apoptosis in CRC cells by inducing cPLA2-dependent mitochondrial ROS production. PMID: 29551681
  5. These findings highlight the positive roles of cPLA2alpha in breast cancer cell growth, survival, migration, and response to chemotherapy. Additionally, this work underscores the therapeutic potential of blocking cPLA2alpha to overcome chemoresistance in breast cancer. PMID: 29307829
  6. These results indicate epigenetic regulation of cPLA2 and the potential for such regulation in the treatment of chronic inflammation. PMID: 26162318
  7. cPLA2alpha may play a key role in renal repair following injury through a PGE2-independent mechanism. PMID: 27554058
  8. This study indicates the potential role of cPLA2alpha in breast cancer metastasis and suggests that this molecule is a promising therapeutic target for breast cancer. PMID: 28383549
  9. These studies suggest that cPLA2alpha expressed by neutrophils, but not epithelial cells, plays a significant role in infection-induced neutrophil transepithelial migration by mediating LTB4 synthesis during migration, thereby amplifying neutrophil recruitment in response to epithelial infection. PMID: 28887431
  10. cPLA2alpha activates PI3K/AKT and inhibits Smad2/3 during epithelial-mesenchymal transition of hepatocellular carcinoma cells. PMID: 28649002
  11. Phospholipase activity is linked to energy metabolism, revealing cPLA2 as a central regulator of both lipidomics and energy flux. PMID: 27133131
  12. This study indicates that among all cytosolic phospholipases A2, specific phospholipase A2 group IVA are the primary enzymes involved in cigarette smoke-induced anomalies in type I and type II lung epithelial cells. PMID: 27528014
  13. A genetic association study in the Quebec City population: Data suggest that total plasma n-6 fatty acid phospholipid levels and C-reactive protein are modulated by SNPs in PLA2G4A and PLA2G6 alone or in combination with fish oil dietary supplementation. PMID: 26525102
  14. cPLA2alpha plays an important role in cell cycle re-entry by quiescent prostate cancer cells. PMID: 26416244
  15. Letter: report instability of cytosolic phospholipase A2alpha variant resulting in severe impairment in platelet arachidonic acid metabolism. PMID: 25904158
  16. Thymocyte maturation can occur independently of cPLA2-alpha. PMID: 25969996
  17. These studies provide a definitive account, demonstrating the fundamental role of cPLA2alpha in eicosanoid formation and cellular responses within the human circulation. PMID: 26183771
  18. The study reports the formation of a multiprotein complex at the G2-to-M transition in vitro and in vivo. Group IVA cytosolic phospholipase A2 (cPLA2-alpha) acts as a bridge in this complex to promote binding of SIRT2 to cyclin A-Cdk2. PMID: 26303530
  19. Case Report/Twin Study: syndromic form of deficiency of cPLA2a , characterized by recurrent GI ulcers and bleeding diathesis, associated with mild inherited deficiency of factor XI. PMID: 25102815
  20. EGF stimulates platelet-activating factor production in ovarian cancer cells in a manner that requires cPLA2. PMID: 24721622
  21. We conclude that cPLA2alpha is required for sustaining AKT phosphorylation at Ser473 and cell proliferation in colorectal cancer cells with PI3K mutation. PMID: 25365190
  22. alphaSN triggered synapse damage via hyperactivation of cPLA2. PMID: 25761116
  23. Suggest retinal pigment epithelium metabolism of 7-ketocholesterol occurs by esterification to fatty acids via cPLA2alpha and SOAT1 followed by selective efflux to HDL. PMID: 25617738
  24. Data indicate 3-(1-Aryl-1H-indol-5-yl)propanoic acids as a potent inhibitor of cytosolic phospholipase A2alpha (cPLA2alpha). PMID: 25102418
  25. cPLA2alpha appears to be an important regulator of central effectors of inflammation and joint destruction, namely MMP3, IL8, COX2, and PGE2. PMID: 24349530
  26. Phospholipase A2 expression in coronary thrombus is associated with recurrence of cardiac events. PMID: 23948114
  27. LMW HA was a potent stimulant of AA release in a time- and dose-dependent manner, inducing cPLA2alpha, ERK1/2, p38, and JNK phosphorylation, as well as activating COX2 expression and prostaglandin (PG) E2 production. PMID: 24366870
  28. Data provide new and important contributions to the understanding of cPLA2alpha regulation at the transcriptional level, with implications for eicosanoid metabolism, cellular signaling, and disease pathogenesis. PMID: 23549331
  29. Mutations in PLA2G4A were identified as a cause of cryptogenic multifocal ulcerating stenosing enteritis in two affected siblings. PMID: 23268370
  30. LacCer is a direct activator of cPLA2alpha. PMID: 23801329
  31. Data detected statistically significant but weak impact of PLA2G4A and PTGS2 gene polymorphisms on niacin flush response in schizophrenia patients. PMID: 23219238
  32. PLA2G4A might serve as a promising target for future therapeutic approaches to gastric cancer combined with COX-2 inhibitors. PMID: 23307260
  33. Results suggest that C2-di-ethyl-ceramide-1-phosphate appeared to inhibit cPLA(2)alpha, probably by interaction with a site in the catalytic domain of the enzyme. PMID: 23043861
  34. The presence of a terminal sialic acid moiety, a rare modification of mammalian glycosylphosphatidylinositol anchors, was essential in the activation of cytosolic phospholipase A2 and synapse damage induced by cross-linked PrPc. PMID: 22895089
  35. The regulation of HT-29 proliferation is mediated by cPLA(2)alpha-dependent PGE(2) production. PGE(2)via EP induces CREB phosphorylation by the PKA pathway and regulates beta-catenin and cyclin D1 cellular localization by the PKB/Akt pathway. PMID: 22728329
  36. A study identified the MAPK/ERK regulated, cytosolic, calcium-dependent PLA2G4A as a novel hepatitis C virus dependency factor; inhibition of PLA2G4A activity reduced core protein abundance at lipid droplets, core envelopment, and secretion of particles. PMID: 22911431
  37. A VE-cadherin-PAR3-alpha-catenin complex regulates the Golgi localization and activity of cytosolic phospholipase A(2)alpha in endothelial cells. PMID: 22398721
  38. The molecular and biological evidence of the involvement of cPLA2s in the pathogenesis of Alzheimer's disease is reviewed. PMID: 22648535
  39. The lipid modifier cPLA2alpha and EHD1 are involved in the vesiculation of CD59-containing endosomes. PMID: 22456504
  40. Immunohistochemical expressions of cPLA(2)alpha in 23 species of human non-small lung cancer and 5 species of human normal lung to assess their clinicopathological relevance. PMID: 22274867
  41. Genetic association studies in populations in Costa Rica: An SNP in PLA2G4A (rs12746200) is associated with myocardial infarction; this association is modulated by dietary factors (i.e., omega-6 fatty acid intake). PMID: 22378731
  42. These results illustrated that cPLA(2)alpha-mediated actin filament rearrangements downstream of Akt activation are required for C. sakazakii invasion into brain endothelial cells. PMID: 22138395
  43. Findings indicate that cPLA2 in the lens epithelial cells is regulated by calcium mobilization and mitogen-activated protein kinases (MAPK) activation; both PDGF mitogenic action and calcium signaling are cPLA(2)alpha-dependent. PMID: 21896865
  44. There is a possible relation between Leptin release and cPLA 2 activity in inflammatory cells induced by LPS. PMID: 21315000
  45. These results provide in vivo evidence for increased expression and activation of cPLA2 in motor neurons, reactive astrocytes, and activated microglia in amyotrophic lateral sclerosis. PMID: 20066429
  46. cPLA(2)alpha gene activation by IL-1beta is dependent on an upstream kinase pathway, enzymatic activation, and downstream 15-lipoxygenase activity: a positive feedback loop. PMID: 21771656
  47. A cPLA2-initiated lipid mediator pathway induces autophagy in a murine macrophage cell line and in human primary monocytes. PMID: 22003202
  48. Mutation of HuR Thr-118 reduced the association between HuR and cPLA(2)alpha mRNA under IL-1beta treatment. PMID: 21862584
  49. These findings demonstrate that specific host factors involving cPLAalpha and cysteinyl LTs contribute to type III GBS penetration of the blood-brain barrier and their contribution involves PKCalpha. PMID: 21825068
  50. There were relatively more cPLA2alpha-positive tumors, as defined by positive staining in >10% of tumor cells (24 of 76 tumors, 32%). PMID: 21198294

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Database Links

HGNC: 9035

OMIM: 600522

KEGG: hsa:5321

STRING: 9606.ENSP00000356436

UniGene: Hs.497200

Involvement In Disease
PLA2G4A mutations resulting in phospholipase A2 deficiency have been found in a patient affected by recurrent episodes of multiple complicated ulcers of the small intestine, not due to cyclooxygenase inhibitors use. Disease features also include platelet dysfunction, and globally decreased eicosanoid synthesis (PubMed:18451993).
Subcellular Location
Cytoplasm. Golgi apparatus membrane. Nucleus envelope.
Tissue Specificity
Expressed in various cells and tissues such as macrophages, neutrophils, fibroblasts and lung endothelium. Expressed in platelets (at protein level).

Q&A

What is PLA2G4A and why is it significant in research?

PLA2G4A is a 100-110 kDa member of the cytosolic phospholipase A2 family. It's physiologically significant because it hydrolyzes membrane phospholipids to generate arachidonic acid, which is subsequently converted into proinflammatory eicosanoids. This enzyme is expressed in various cell types including endothelium, smooth muscle, macrophages, neutrophils, fibroblasts, mast cells, and platelets. Its expression can be induced in specific contexts, and tumor cells often serve as sources for cPLA2α activity. The protein contains a phospholipid-binding C2 domain (amino acids 1-178) and a catalytic PLA2c domain (amino acids 140-740) .

What is the difference between human and mouse PLA2G4A?

Full-length human PLA2G4A (749 amino acids) shares 94% amino acid sequence identity with mouse PLA2G4A. This high conservation allows certain antibodies, such as the AF6659 antibody, to detect both human and mouse variants. When selecting an antibody for cross-species studies, researchers should verify this cross-reactivity in the product documentation .

What are the recommended applications for PLA2G4A antibodies?

PLA2G4A antibodies are validated for several applications including:

ApplicationRecommended DilutionSample Types
Western Blot (WB)1:1000-1:4000HeLa cells, NIH-3T3 cells
Immunohistochemistry (IHC)1:50-1:500Human colon cancer tissue
ELISAAccording to protocolVarious

For optimal results, each antibody should be titrated for specific experimental systems .

What are the optimal conditions for Western blot detection of PLA2G4A?

For Western blot analysis of PLA2G4A:

  • Use PVDF membrane for optimal protein binding

  • Run samples under reducing conditions

  • Expect bands at approximately 100-110 kDa

  • For the Proteintech antibody (28924-1-AP), use a dilution of 1:1000-1:4000

  • For the R&D Systems antibody (AF6659), a concentration of 0.1 μg/mL is recommended

  • Use appropriate HRP-conjugated secondary antibodies

  • Use Immunoblot Buffer Group 1 for optimal results when using AF6659

Note that phosphorylation may increase the apparent molecular weight of cPLA2α in SDS-PAGE to about 100 kDa compared to its calculated weight of 85 kDa .

How should I prepare samples for immunohistochemical detection of PLA2G4A?

For IHC applications using paraffin-embedded tissue sections:

  • Use immersion-fixed paraffin-embedded sections

  • For the AF6659 antibody, use at 5 μg/mL and incubate overnight at 4°C

  • For the Proteintech antibody (28924-1-AP), dilute 1:50-1:500

  • Use antigen retrieval with TE buffer pH 9.0 (alternatively, citrate buffer pH 6.0 may be used)

  • For visualization, use appropriate HRP-DAB detection systems

  • Counterstain with hematoxylin for contrast

  • Expect cytoplasmic localization of PLA2G4A staining

Following these protocols will help achieve specific staining of PLA2G4A in tissue samples .

How does PLA2G4A expression influence tumor progression in colorectal cancer?

The mechanism appears to involve immunomodulation: RSCRC with abnormal PLA2G4A expression educates γδ T cells into CD39+ γδ regulatory T cells (Tregs), promoting tumor progression and metastasis. In experimental models, overexpression of Pla2g4a in CT26 cells induced CD39+ γδ Tregs, inhibiting antitumor immune responses. This highlights the complex interaction between cancer cells and immune cells that depends on the primary tumor site .

How does PLA2G4A activation influence its cellular localization and function?

PLA2G4A undergoes a complex activation process that directly affects its function:

  • In resting cells, PLA2G4A resides in the cytosol

  • Upon activation by various agonists, Ca²⁺ binds to the N-terminal C2 domain

  • This promotes translocation from the cytoplasm to endomembranes including the Golgi, ER, and nuclear membrane

  • At these membrane sites, PLA2G4A hydrolyzes the acyl bond of membrane phospholipids

  • This produces arachidonic acid (AA) and lysophosphatidylcholine

  • AA is subsequently converted into eicosanoids, prostaglandins, leukotrienes, and thromboxane

  • These lipid mediators regulate various processes including T cell differentiation and inflammatory responses

Phosphorylation, particularly at Ser505 and Ser727, contributes significantly to PLA2G4A activation. There are at least five other phosphorylation sites that may influence its activity and function .

What are common challenges in detecting PLA2G4A and how can they be addressed?

When working with PLA2G4A antibodies, researchers may encounter several challenges:

ChallengePotential Solution
Multiple bands in Western blotVerify specificity with appropriate controls (KO/KD validation); optimize antibody concentration; consider post-translational modifications
Weak signalIncrease antibody concentration; extend incubation time; enhance antigen retrieval for IHC; increase protein loading for WB
High backgroundUse more stringent washing; decrease antibody concentration; optimize blocking conditions
Inconsistent molecular weightNote that phosphorylation can increase apparent MW to ~100 kDa from calculated 85 kDa
Cross-reactivity concernsValidate with species-specific controls; consider using monoclonal antibodies for higher specificity

For optimal results, it's recommended to validate the antibody in your specific experimental system and include appropriate positive and negative controls .

How can I differentiate between activated and non-activated forms of PLA2G4A?

Distinguishing between activated and non-activated PLA2G4A requires attention to several factors:

  • Phosphorylation status: Use phospho-specific antibodies targeting key sites (Ser505, Ser727)

  • Subcellular localization: Non-activated PLA2G4A is predominantly cytosolic, while activated forms translocate to membranes

  • Molecular weight shifts: Phosphorylation can increase the apparent molecular weight in SDS-PAGE

  • Functional assays: Measure enzymatic activity through phospholipid hydrolysis or arachidonic acid release assays

  • Downstream products: Detect eicosanoid production as an indirect measure of PLA2G4A activation

Combining these approaches provides more reliable assessment of PLA2G4A activation state than any single method alone .

How is PLA2G4A involved in immune modulation and what are the implications for cancer immunotherapy?

Recent research has uncovered a significant role for PLA2G4A in immune modulation, particularly in the context of cancer:

  • In colorectal cancer, PLA2G4A expression influences γδ T cell phenotype and function

  • Overexpression of PLA2G4A induces CD39+ γδ Tregs that predominantly produce IL-17A

  • These CD39+ γδ Tregs suppress antitumor immune responses

  • The immunomodulatory effects appear to be site-specific, with different outcomes in right-sided versus left-sided colorectal cancers

  • Silencing PLA2G4A can reduce CD39 expression on γδ T cells and restore their antitumor function

These findings suggest targeting PLA2G4A might enhance antitumor immunity by preventing the formation of immunosuppressive γδ Tregs. This could potentially complement existing immunotherapies, particularly in patients with high PLA2G4A expression. Further research is needed to determine whether PLA2G4A inhibitors could augment responses to checkpoint inhibitors or other immunotherapeutic approaches .

What is the relationship between PLA2G4A expression and microsatellite instability in colorectal cancer?

Analysis of GEPIA2 datasets has revealed that PLA2G4A expression levels in colorectal tumors correlate with microsatellite instability status:

  • Microsatellite instability-high (MSI-H) colorectal tumors show significantly higher expression of PLA2G4A compared to microsatellite instability-low (MSI-L) and microsatellite stable (MSS) tumors

  • This suggests PLA2G4A may play a role in the distinct biology of MSI-H tumors

  • The connection between microsatellite instability and immunomodulatory effects of PLA2G4A requires further investigation

  • This relationship could have implications for patient stratification and treatment selection

Understanding this relationship could help predict which patients might benefit from targeting PLA2G4A or its downstream pathways in combination with existing therapies for MSI-H colorectal cancers .

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