PLPZETA2 Antibody

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Description

PLBL2 Antibodies in Biopharmaceutical Context

PLBL2 is a host cell protein (HCP) that co-purifies during monoclonal antibody (mAb) production. Key findings include:

  • Incidence: ~90% of subjects developed anti-PLBL2 antibodies when exposed to lebrikizumab (an anti-IL13 mAb) containing PLBL2 impurities .

  • Clinical Impact:

    • No correlation between anti-PLBL2 antibodies and adverse events .

    • No adjuvant effect on anti-drug antibody formation .

    • Subsequent reduction of PLBL2 impurities decreased immune responses in phase III trials .

Table 1: Anti-PLBL2 Antibody Clinical Observations

ParameterObservationSource
Seroprevalence90% in phase I/II trials
Safety CorrelationNone with placebo/drug groups
Drug ImmunogenicityUnaffected by PLBL2 co-exposure

PLP2 in Cancer and Immunology

PLP2 (proteolipid protein 2) is an ion channel implicated in tumorigenesis and immune modulation:

  • Expression: Overexpressed in 21 cancer types, including glioblastoma (GBM), lung adenocarcinoma, and breast cancer .

  • Immune Correlation:

    • Positive association with CD4+ T cells (ρ=0.27, p=0.001), neutrophils (ρ=0.31, p=9.51e-5), and macrophages (ρ=0.2, p=0.016) in GBM .

    • Linked to PD-L1 upregulation in tumor microenvironments .

Table 2: PLP2 Correlation with Immune Infiltration in GBM

Immune Cell TypeSpearman’s ρp-valueSource
CD4+ T cells0.270.001
Neutrophils0.319.51 × 10⁻⁵
Myeloid dendritic cells0.484.08 × 10⁻¹⁰
Macrophages0.200.016

Functional Implications of PLP2 Antibodies

  • Therapeutic Potential: PLP2-derived peptides (e.g., Rb4) exhibit antimelanoma activity dependent on immune activation .

  • Mechanistic Role:

    • Facilitates immune evasion in Kaposi’s sarcoma-associated herpesvirus .

    • Modulates endoplasmic reticulum stress responses under hypoxia .

Comparative Analysis of PLBL2 vs. PLP2

FeaturePLBL2PLP2
Primary ContextBiopharmaceutical impuritiesOncogenesis, immune modulation
Antibody Prevalence90% in exposed cohorts Not directly reported
Clinical RelevanceProcess-related impurity controlPrognostic biomarker candidate
Therapeutic TargetingMinimized in later-phase drugs Experimental (e.g., Rb4 peptide)

Research Gaps and Opportunities

  • PLPZETA2 Clarification: No peer-reviewed studies explicitly reference "PLPZETA2." Standardization of nomenclature is critical to avoid conflating PLP2, PLBL2, or unrelated targets.

  • Antibody Engineering: Advances in Fc glycosylation (e.g., sialylation, fucosylation) could enhance effector functions against PLP2-expressing tumors .

  • Diagnostic Utility: PLP2’s correlation with PD-L1 suggests utility in predicting immunotherapy responsiveness .

Product Specs

Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Made-to-order (14-16 weeks)
Synonyms
PLPZETA2 antibody; PLDP2 antibody; At3g05630 antibody; F18C1.10 antibody; Phospholipase D zeta 2 antibody; PLDzeta2 antibody; EC 3.1.4.4 antibody; Phospholipase D p2 antibody; AtPLDp2 antibody; Phospholipase D2 PHOX and PX-containing domain protein antibody
Target Names
PLPZETA2
Uniprot No.

Target Background

Function
PLDzeta2 is an enzyme that hydrolyzes glycerol-phospholipids at the terminal phosphodiesteric bond, producing phosphatidic acids (PA). It exhibits selectivity for phosphatidylcholine. PLDzeta2 plays a crucial role in regulating vesicle trafficking and auxin responses, being essential for the normal cycling of PIN-2 containing vesicles. Furthermore, it contributes to the supply of inorganic phosphorus for cell metabolism and diacylglycerol moieties for galactolipid synthesis in phosphorus-starved roots. PLDzeta2 is also involved in root elongation during phosphate limitation.
Gene References Into Functions
  1. Under salt stress, the efficiency of photosystem II, assessed by measuring the chlorophyll fluorescence ratio (F v/ m ratio), was significantly decreased in pldzeta1. This finding suggests that PLDzeta2 plays a vital role in determining Arabidopsis sensitivity to salt stress, enabling fine-tuning of ion transport and antioxidant responses. PMID: 28667438
  2. AtPLDzeta2 participates in phosphatidic acids production through a calcium signaling pathway, while AtPLDzeta1 is more prominently involved in reactive oxygen species signaling. PMID: 28834646
  3. The PLDZ2 promoter contains a transcriptional enhancer that imparts Pi responsiveness to a minimal, inactive 35S promoter. This enhancer also exhibits cytokinin and sucrose responsiveness observed for the intact PLDZ2 promoter. PMID: 22210906
  4. A variant of the PHR1 binding site is highly enriched in the Arabidopsis phosphate-responsive phospholipase DZ2 coexpression network. PMID: 22836502
  5. PLDzeta2 responds to drought through ABA signaling in the root cap and accelerates root hydrotropism by suppressing root gravitropism. PMID: 19915862
  6. PLDzeta2 plays a significant role in regulating root development in response to nutrient limitation. PMID: 16384909
  7. The pldz2 mutant exhibits a deficiency in phospholipid hydrolysis and a reduced capacity to accumulate galactolipids under limiting Pi conditions. PMID: 16617110
  8. Hydrolysis of phosphatidylcholine by PLD zetas during phosphorus starvation contributes to the supply of inorganic phosphorus in A. thaliana. PMID: 16891548
  9. PLDzeta2 and its product, phosphatidic acid (PA), are essential for the normal cycling of PIN2-containing vesicles and for their function in auxin transport and distribution, ultimately influencing auxin responses. PMID: 17259265
  10. AtPLDzeta2 localizes to the tonoplast, and its Nter regulatory domain is sufficient for its sorting. Under phosphate deprivation, AtPLDzeta2 remains located in the tonoplast, but its distribution becomes uneven. PMID: 18242181

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Database Links

KEGG: ath:AT3G05630

STRING: 3702.AT3G05630.1

UniGene: At.40640

Protein Families
Phospholipase D family, PXPH-PLD subfamily
Tissue Specificity
Expressed in seedlings, roots, leaves, stems and flowers. Highest expression in roots. Detected only in the meristematic regions up to 4 days after germination and then at later stages in all tissues.

Q&A

FAQs for Researchers: PLCG2 (PLPZETA2) Antibody Applications in Academic Research

Advanced Research Challenges

  • How to resolve discrepancies in PLCG2 antibody performance across cell lines or tissues?

    • Conduct cell-type-specific validation due to PLCG2’s variable expression in immune cells (e.g., B cells vs. mast cells) .

    • Use multiple antibodies targeting distinct epitopes to confirm findings, as post-translational modifications (e.g., phosphorylation) may affect binding .

  • What strategies address PLCG2 antibody cross-reactivity in heterologous expression systems?

    • Employ silencing RNA (siRNA) to knock down endogenous PLCG2 and verify antibody specificity in transfected cells .

    • Pair with mass spectrometry to identify off-target proteins in immunoprecipitates .

  • How can computational modeling improve PLCG2 antibody design for mutant isoforms?

    • Use molecular docking simulations to predict binding affinity changes caused by mutations (e.g., PLCG2-associated antibody deficiency variants) .

    • Validate predictions via phage-display libraries to screen for mutants resistant to antibody binding .

Methodological Insights from Recent Studies

Table 1: Antibody Performance in PLCG2 Detection (Adapted from )

ApplicationSuccess Rate (%)Key Criteria MetLimitations
Western Blot82KO validation, linearityBatch-dependent variability
Immunofluorescence68Subcellular localizationLow signal in fixed tissues
Immunoprecipitation75Target enrichmentNon-specific binding

Table 2: Impact of PLCG2 Mutations on Antibody Binding (Adapted from )

MutationFunctional EffectAssay Compatibility
R28WConstitutive activationWB, IF (cytoplasmic)
L845PImpaired enzyme activityIP, functional assays
S707YTemperature-sensitive signalingIF (requires cooling)

Data Contradiction Analysis

  • How to interpret conflicting PLCG2 expression data in autoimmune vs. neurodegenerative contexts?

    • Consider disease-specific post-translational modifications (e.g., phosphorylation at Tyr753) that may alter antibody accessibility .

    • Cross-validate with RNA-seq or CRISPR-Cas9 knockouts to rule out antibody artifacts .

  • Why do some PLCG2 antibodies fail in extracellular matrix (ECM) studies?

    • PLCG2 is primarily cytoplasmic; ECM localization may reflect artifacts from tissue processing or non-specific binding .

    • Combine subcellular fractionation with antibody validation to isolate true signals .

Experimental Design Recommendations

  • For longitudinal studies, standardize antibody lots and storage conditions (-80°C aliquots) to minimize variability .

  • In PLAID models, simulate temperature gradients (e.g., 25–32°C) to assess PLCG2 antibody performance under mutation-specific conditions .

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