STAT4 Antibody
Product Specs
Target Background
- A recent study suggests that genetic variations in the GATA3 transcription factor, rather than STAT4, may be associated with the risk of type 2 diabetes in the Bangladeshi population. PMID: 30044774
- While the STAT4 gene's rs7574865 and rs7601754 SNPs are linked to adult SLE risk in the Iranian population, their lack of association with juvenile systemic lupus erythematosus (JSLE) in the same population points to distinct genetic backgrounds between these conditions. PMID: 29276866
- Research has confirmed the association of the STAT4 rs7574865 polymorphism with rheumatoid arthritis, and for the first time, indicated an association with rheumatoid factor and anti-cyclic citrullinated peptide antibodies positivity. However, no significant correlations were found between STAT4 variants and serum neopterin or disease activity parameters. PMID: 28424905
- An analysis of five STAT4 SNPs in individuals with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls revealed significant associations with NMOSD for four SNPs: rs7574865 T; rs10181656 G; rs10168266 T; and rs13426947 A. The minor alleles of these SNPs were associated with an increased risk of NMOSD. Conversely, the rs7601754 G allele exhibited a protective effect against NMOSD. PMID: 28852993
- Evidence suggests that STAT4 plays a role in enabling the normal and timely division of cells during mitosis. PMID: 28516569
- A genome-wide association study identified a locus in STAT4, rs13390936, associated with nontyphoidal Salmonella bacteremia. PMID: 29523850
- Despite its association with adult SLE, the rs7601754 SNP in the STAT4 gene was not found to be associated with juvenile rheumatoid arthritis (JRA) in an Iranian population. PMID: 28524764
- STAT4 has been identified as a novel transcriptional regulator of p66Shc in both normal and chronic lymphocytic leukemia B cells. PMID: 27494881
- Genetic variants in IL13 (rs20541 AA) and STAT4 (rs925847 TT) have been identified as potential genomic biomarkers for predicting lower pulmonary function. While high-dose inhaled corticosteroids (ICSs) may inhibit airway remodelling progression in asthmatic patients with the IL13 AA variant, the STAT4 TT variant did not show a response to high-dose ICSs. PMID: 26765219
- A significant correlation has been observed between STAT4 and IFNG mRNA expression levels. PMID: 29187449
- Studies have shown that STAT4 variants play a significant role in hepatitis B virus (HBV) infection and clearance in the Chinese Han population. PMID: 27444301
- The STAT4 rs7574865G/T polymorphism is associated with an increased risk of rheumatoid arthritis and systemic lupus erythematosus in Mexican women. PMID: 27178308
- The STAT4_rs7574865 TT genotype has been associated with the presence of actively inflamed joints and extra-articular damage in patients with Juvenile Idiopathic Arthritis. PMID: 28145159
- Research has found that activated STAT4 is overexpressed in epithelial cells of ovarian cancer and promotes ovarian cancer metastasis through tumor-derived Wnt7a-induced activation of cancer-associated fibroblasts. PMID: 28114283
- The STAT4 rs7574865 gene polymorphism is associated with the susceptibility of primary biliary cirrhosis in the Han population of Jiangsu province. PMID: 28395724
- Studies in the Russian population suggest that the STAT4 gene plays a significant role in the predisposition to Systemic sclerosis and its associated phenotypes, such as interstitial lung disease, cardiac injury, and seropositivity for anti-topoisomerase I antibodies. PMID: 28631694
- Research has highlighted the specific and dominant contribution of STAT4 in the hematopoietic compartment to metabolic health and inflammation in diet-induced obesity. PMID: 28400678
- While SNPs in STAT4, PTPN2, PSORS1C1, and TRAF3IP2 have been associated with response to tumor necrosis factor inhibitor (TNF-i) treatment in rheumatoid arthritis patients, these findings need to be validated in a larger population. PMID: 28107378
- STAT4 has been demonstrated to act as a transcriptional repressor in response to interferon-alpha/beta signaling in human T cells. This highlights the unique ability of this cytokine to acutely block the expression of an inflammatory cytokine. PMID: 26990433
- The rs7574865 SNP in the STAT-4 gene was found to be associated with an increased risk of developing rheumatoid arthritis, while the rs1800872 SNP in the IL-10 gene showed a protective effect. PMID: 27342690
- The STAT4 rs7574865 polymorphism is associated with rheumatoid arthritis and disease activity in a Mexican population, but not with anti-CCP antibody levels. PMID: 27234231
- Studies have shown that STAT4 gene polymorphisms can impact clinical outcomes of pediatric acute leukemia patients following hematopoietic stem cell transplantation. PMID: 27960128
- STAT4 gene polymorphisms have been found to be associated with ankylosing spondylitis in Southwest China. PMID: 27394003
- For the first time, research has demonstrated a significant association between STAT4 rs7582694 alleles and genotypes and susceptibility to endometriosis in a population. PMID: 27235632
- The STAT4-rs7574865 polymorphism has been clearly associated with the risk of Rheumatoid Arthritis in the Western Algerian population. PMID: 25351936
- Research has demonstrated that the STAT4 rs7574865 and IRF5 rs2004640G/T substitutions are associated with susceptibility to systemic sclerosis. PMID: 26712637
- While STAT4 and IFIH1 SNPs were not found to be associated with type 1 diabetes in a Brazilian population, they may play a role in susceptibility to T1D on a larger global scale. PMID: 26782418
- The SNP rs7574865 in STAT4 may contribute to the progression to Hepatocellular Carcinoma. PMID: 26745093
- Five SNPs (rs7574865 in STAT4, rs9267673 near C2, rs2647073 and rs3997872 near HLA-DRB1 and rs9275319 near HLA-DQ) have been found to be significantly associated with the risk of HBV-related liver cancer. PMID: 26538132
- A significant association has been observed between STAT4 rs7574865 polymorphism and inflammatory bowel disease (IBD) susceptibility in the overall population. PMID: 26066297
- Genetic variation in the STAT4 protein has been identified as a prognostic factor predicting the effectiveness of interferon-alpha therapy in chronic hepatitis B. PMID: 26704347
- The presence of the rs7574865 T allele enhances STAT4 mRNA transcription and protein expression. PMID: 26569609
- The STAT4 rs7574865 polymorphism may be associated with a significantly reduced risk of HBV-induced hepatocellular carcinoma in Asian populations. PMID: 25178516
- A meta-analysis has shown that gene polymorphisms in STAT4, along with Ptpn22 polymorphism, contribute to the susceptibility to rheumatoid arthritis in all major ethnic groups. PMID: 25963842
- Significant associations have been reported between alleles of two STAT4 markers and autoimmune Addison's disease, along with nominal associations between alleles at GATA3 and this condition. PMID: 24614117
- A replication study in a Korean population indicated that rs7574865 in STAT4 and rs9275319 in HLA-DQ were not associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma. PMID: 25913043
- CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 have been identified as bona fide susceptibility genes for Behcet's disease. PMID: 26097239
- The STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms have been identified as susceptibility factors for juvenile idiopathic arthritis (JIA). PMID: 25781893
- The STAT4 minor allele may be associated with the spontaneous clearance of HBV, while the major allele may be associated with the progression of HBV-related liver disease. PMID: 25829184
- STAT4 may inhibit hepatocellular carcinoma (HCC) development by modulating HCC cell proliferation. PMID: 25852285
- A meta-analysis has shown that the STAT4 rs7574865 polymorphism confers susceptibility to rheumatoid arthritis in major ethnic groups. PMID: 24751105
- Studies have provided evidence for a higher risk of developing pericarditis with STAT4 genotypes, and an association between HCP5 rs3099844 and anti-Ro/SSA antibodies in Italian systemic lupus erythematosus patients. PMID: 25369137
- The STAT4 rs7574865 polymorphism appears to be specific to Tibetans in relation to hepatitis B virus natural clearance. PMID: 25041342
- The STAT4 rs7574865 polymorphism was not found to be correlated with hepatitis B virus infection susceptibility or natural clearance, and its role in hepatocellular carcinoma development remains ambiguous. PMID: 25365208
- The loss of STAT4 expression and associated switch to Th2 phenotype during Mycosis Fungoides progression may be driven by aberrant histone acetylation and/or upregulation of the oncogenic miR-155 microRNA. PMID: 25486484
- Increased expression of STAT4 has been found to be positively correlated with the depth of invasion in colorectal cancer patients. PMID: 25864744
- Research has reported the association of 14q32.11 (EFCAB11) with Hepatocellular carcinoma in the Chinese Han population, and revealed the genetic interaction between STAT4 (2q32.2-q32.3) and EFCAB11 (14q32.11) in Hepatocellular carcinoma. PMID: 25665738
- The STAT4 rs7574865/rs10181656 polymorphisms have been found to increase the risk of autoimmune thyroid diseases in a Chinese population. PMID: 25019342
- Rheumatoid arthritis cases showed a significantly higher frequency of STAT4 T allele carriage (GT+TT genotypes) compared to controls. PMID: 24979672
- STAT4 plays a crucial role in the function of innate and adaptive immune cells. Dysregulated expression and aberrant activation of STAT4 have been observed in many human autoimmune conditions. PMID: 24844303
Q&A
What is STAT4 and why is it an important research target?
STAT4 is a member of the Signal Transducer and Activator of Transcription (STAT) family that localizes to the cytoplasm and plays a crucial role in immune signaling. This 86 kDa (748 amino acid) protein is phosphorylated after various cytokines bind to membrane receptors, which leads to dimerization and nuclear translocation where it regulates gene expression . STAT4 is particularly important because it mediates IL-12, IL-23, and type-1 interferon cytokine signals in T-cells and monocytes .
STAT4 is essential for:
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Promoting cellular-mediated immune responses via Th1 cell differentiation
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Regulating IFN-γ production in immune cells
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Mediating inflammatory and autoimmune processes
STAT4 has become a significant research target because its dysregulation is implicated in numerous autoimmune and inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, psoriasis, and inflammatory bowel diseases .
What are the key applications of STAT4 antibodies in research?
STAT4 antibodies are versatile tools that can be employed in multiple experimental techniques:
Each application requires specific optimization for your experimental system, and the chosen antibody should be validated for the specific application .
How do I select between phospho-specific and total STAT4 antibodies?
The choice between phospho-specific and total STAT4 antibodies depends on your research question:
Total STAT4 antibodies:
Phospho-STAT4 antibodies:
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Specifically recognize STAT4 when phosphorylated at Tyr693
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Essential for studying STAT4 activation and signaling dynamics
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Crucial for monitoring JAK-STAT pathway activity
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Particularly important when studying cytokine responses, as phosphorylation at Tyr693 is associated with STAT4 activation following IL-12 or type 1 IFN stimulation
For comprehensive signaling studies, it's often valuable to use both types of antibodies in parallel to determine both the total protein levels and the proportion of activated STAT4 .
What factors should I consider when choosing between monoclonal and polyclonal STAT4 antibodies?
For critical quantitative experiments or those requiring precise epitope recognition, monoclonal antibodies provide better reproducibility. For detection of low-abundance targets or when signal amplification is needed, polyclonal antibodies may be advantageous .
How can I optimize STAT4 antibody use for detecting activation in response to different cytokines?
STAT4 activation occurs in response to different cytokines, primarily IL-12 and type 1 interferons (IFN-α/β). Optimizing detection requires careful experimental design:
For IL-12-induced activation:
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Pre-stimulate cells with IL-12 (typically 10-20 ng/ml) for 15-30 minutes
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Immediately fix cells to preserve phosphorylation state
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Use phospho-STAT4 (Tyr693) specific antibodies for detection
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Note that IL-12 induces stronger and more sustained STAT4 phosphorylation than IFN-α in mouse models
For IFN-induced activation:
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Different dynamics exist between human and mouse cells
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In mice, IFN-α phosphorylation of STAT4 is weaker and more transient than IL-12-induced phosphorylation
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In humans, IFN-α significantly contributes to Th1 development via STAT4 activation
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Time course experiments (5, 15, 30, 60 minutes) are recommended to capture potentially transient activation
Methodological considerations:
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For flow cytometry, use Protocol C: Two-step protocol with Fixation/Methanol (Protocol A or B are not suitable)
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Include both positive controls (IL-12 stimulated cells) and negative controls (JAK inhibitor treated cells)
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Consider cell-type specific differences in STAT4 expression and activation kinetics (e.g., STAT4 is activated by IL-2 in NK cells but not in T cells)
What technical considerations are important for phospho-STAT4 detection in complex tissue samples?
Detecting phosphorylated STAT4 in tissue samples presents unique challenges:
Sample preparation:
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Rapid fixation is critical to preserve phosphorylation states
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For tissues, snap-freezing followed by careful thawing in buffer containing phosphatase inhibitors is recommended
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Fresh samples yield more reliable phospho-STAT4 results than archived samples
Methodological approaches:
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For immunohistochemistry, antigen retrieval is critical (typically heat-mediated in citrate buffer pH 6.0)
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Signal amplification methods may be necessary for low abundance detection
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Multiplex staining can help identify specific cell populations with activated STAT4
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For flow cytometry of tissue-derived cells, specialized fixation and permeabilization protocols are necessary
Controls and validation:
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Include tissues from STAT4-deficient animals as negative controls
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Use phosphatase treatment of a sample split as a control for phospho-specificity
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Consider dual staining for total STAT4 and phospho-STAT4 to normalize signals
How can I use STAT4 antibodies to study STAT4 polymorphisms associated with disease risk?
STAT4 polymorphisms, particularly rs7574865, have been associated with various autoimmune diseases and hepatocellular carcinoma risk . To study these associations:
Experimental approaches:
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Western blotting can detect potential differences in protein expression levels associated with SNPs
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ChIP assays using STAT4 antibodies can reveal altered DNA binding patterns
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Flow cytometry with phospho-STAT4 antibodies can assess differences in activation dynamics
Methodological considerations:
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For rs7574865 SNP (associated with lower mRNA levels of STAT4), compare STAT4 protein levels in cells with different genotypes
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Stimulate cells with cytokines and measure phospho-STAT4 dynamics in different genotype backgrounds
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Consider using CRISPR/Cas9 to generate isogenic cell lines differing only in STAT4 genotype
Data interpretation:
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Correlate measured STAT4 protein levels or activation patterns with genotype data
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Consider analyzing both basal and stimulated conditions
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Evaluate the impact of polymorphisms on downstream effector functions like IFN-γ production
What are best practices for troubleshooting inconsistent STAT4 antibody results across experimental systems?
When encountering inconsistent results with STAT4 antibodies:
Antibody validation:
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Confirm antibody specificity using STAT4 knockout/knockdown controls
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Test multiple antibody clones targeting different epitopes
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Verify antibody reactivity with your species of interest (human, mouse, rat)
Technical optimization:
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For western blots, optimize lysis conditions to ensure complete protein extraction
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For flow cytometry, carefully optimize fixation and permeabilization protocols
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For immunofluorescence, test different fixation methods (PFA vs. methanol)
Biological considerations:
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Remember that STAT4 expression is cell-type specific and can be induced by certain stimuli
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Consider the presence of different STAT4 isoforms (STAT4α and STAT4β)
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Account for potential post-translational modifications affecting epitope recognition
Methodological approach:
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Implement a systematic optimization approach changing one variable at a time
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Document all experimental conditions meticulously
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Consider sending samples for analysis with standardized protocols at a core facility
How can STAT4 antibodies be used to study the complex interplay between STAT4 and other transcription factors?
STAT4 functions within a complex network of transcription factors and co-regulators:
Co-immunoprecipitation approaches:
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Use STAT4 antibodies for immunoprecipitation followed by western blotting for potential interaction partners
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Consider crosslinking approaches for capturing transient interactions
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Optimize lysis conditions to preserve protein-protein interactions
ChIP-seq analysis:
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STAT4 antibodies can be used in ChIP-seq to identify genome-wide binding sites
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Compare STAT4 binding with other factors (STAT1, STAT3) to identify co-regulatory regions
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Validated for this purpose: Stat4 (C46B10) Rabbit mAb has been tested for ChIP-seq applications
Proximity ligation assays:
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Combine STAT4 antibodies with antibodies against potential interacting partners
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Visualize protein-protein interactions in situ with subcellular resolution
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Particularly useful for studying dynamics of STAT4 interactions with JAKs or other STATs
Sequential ChIP (Re-ChIP):
