MAP3K5 (Ab-83) Antibody
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Product Specs
Form
Supplied at 1.0 mg/mL in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150 mM NaCl, 0.02% sodium azide and 50% glycerol.
Lead Time
Typically, we can ship the products within 1-3 business days after receiving your order. Delivery time may vary depending on the method of purchase or location. For specific delivery times, please consult your local distributors.
Synonyms
Apoptosis signal regulating kinase 1 antibody; Apoptosis signal-regulating kinase 1 antibody; ASK 1 antibody; ASK-1 antibody; ASK1 antibody; M3K5 antibody; M3K5_HUMAN antibody; MAP/ERK kinase kinase 5 antibody; MAP3K5 antibody; MAPK/ERK kinase kinase 5 antibody; MAPKKK5 antibody; MEK kinase 5 antibody; MEKK 5 antibody; MEKK5 antibody; Mitogen activated protein kinase kinase kinase 5 antibody; Mitogen-activated protein kinase kinase kinase 5 antibody
Target Names
Uniprot No.
Target Background
Function
Apoptosis signal-regulating kinase 1 (ASK1), also known as MAP3K5, is a serine/threonine kinase. It is an essential component of the mitogen-activated protein kinase (MAPK) signal transduction pathway, which plays a vital role in cellular responses to environmental changes. ASK1 mediates signaling for crucial cellular processes such as differentiation and survival. It is also a key player in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. ASK1 is critical for the innate immune response, which is essential for host defense against a wide range of pathogens. It mediates signal transduction of various stressors, including oxidative stress and receptor-mediated inflammatory signals such as tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, ASK1 acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade. This occurs through the phosphorylation and activation of several MAP kinase kinases, including MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6, and MAP2K7/MKK7. These MAP2Ks, in turn, activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).
Gene References Into Functions
- Advanced glycation end products significantly activated ASK1, MKK3, and MKK6, leading to the activation of p38 MAPK, which resulted in upregulated fibrotic response in human coronary smooth muscle cells. PMID: 30305582
- ASK1 transcriptional upregulation molecularly defines a metabolically detrimental obese sub-phenotype. PMID: 28702328
- Knockdown of miR-20a enhanced the sensitivity of colorectal cancer cells to cisplatin through the ROS/ASK1/JNK pathway. PMID: 29940575
- These findings offer insight into the positive regulation of Akt signaling through P2Y12 phosphorylation, as well as MAPK signaling in platelets by ASK1. PMID: 28753204
- Cold stress-induced ferroptosis involves the ASK1-p38 pathway. PMID: 28887319
- TRIM48 Promotes ASK1 Activation and Cell Death through Ubiquitination-Dependent Degradation of the ASK1-Negative Regulator PRMT1 PMID: 29186683
- These findings indicate that chaetocin arrests the cell cycle and induces apoptosis by regulating the reactive oxygen species-mediated ASK-1/JNK signaling pathways. PMID: 28849240
- Findings provide evidence that ASK-1 expression is regulated by SLC35F2, which exerts its oncogenic effect on papillary thyroid carcinoma progression through the activation of TGFBR-1 and ASK-1. PMID: 29274137
- Co-administration of acetaminophen and 5'-AMP significantly ameliorated APAP-induced hepatotoxicity in mice. This was triggered by attenuating apoptosis signal-regulated kinase 1 (ASK1) methylation and increasing ubiquitination-mediated ASK1 protein degradation. PMID: 28031524
- The anti-cancer mechanism for the AgNPs may be involved in activating the ASK1-JNK/p38-Caspase-3 pathway. PMID: 29381295
- TRAF1 functions as a positive regulator of insulin resistance, inflammation, and hepatic steatosis dependent on the activation of the ASK1-P38/JNK axis. PMID: 26860405
- LRRK2-induced apoptosis was suppressed by ASK1 inhibition in neuronal stem cells derived from patients with Parkinson's disease (PD). These results clearly indicate that LRRK2 acts as an upstream kinase in the ASK1 pathway and plays an important role in the pathogenesis of PD. PMID: 28888991
- Apoptosis signal-regulating kinase 1 (ASK1) expression was dramatically suppressed and correlated with hepatocyte nuclear factor 4alpha (HNF4alpha) levels in hepatocellular carcinoma (HCC) tissues. PMID: 27050273
- ASK1 phosphorylated and stabilized TLX, which led to the induction of HIF-1alpha, and its downstream VEGF-A in an Akt dependent manner. PMID: 27890558
- CD40 activation resulted in the down-regulation of Thioredoxin (Trx)-1 to permit ASK1 activation and apoptosis. Although soluble receptor agonist alone could not induce death, combinatorial treatment incorporating soluble CD40 agonist and pharmacological inhibition of Trx-1 was functionally equivalent to the signal triggered by mCD40L. PMID: 27869172
- These results suggest that the platelet Ask1 plays an important role in the regulation of hemostasis and thrombosis. PMID: 28028021
- From the two catalytic cysteines of TRX1, the residue C32 is responsible for the high-affinity binding of TRX1 to the ASK1-TRX-binding domain in reducing conditions. PMID: 27588831
- Shotgun mass spectrometry and manual validation identified 12 distinct ASK1 phosphosites. Targeted parallel reaction monitoring assays were used to track the phosphorylation dynamics of each confirmed site in response to treatment. PMID: 27989136
- Phosphorus NMR and time-resolved tryptophan fluorescence measurements suggest that 14-3-3zeta interacts with the kinase domain of ASK1 in close proximity to its active site. This interaction might block its accessibility and/or affect its conformation. PMID: 27514745
- The ASK1 MAP kinase signaling cascade is an important regulator of chondrocyte terminal differentiation. PMID: 26405834
- Pretreatment by IRE1 agonist tunicamycin or JNK agonist anisomycin attenuated the effect of psoralen on osteoporotic osteoblasts. Psoralen inhibited apoptosis of osteoporotic osteoblasts by regulating the IRE1-ASK1-JNK pathway. PMID: 28349059
- Our results thus suggest that GSK-3beta is a key factor involved in ASK1 activation and reactive oxygen species-induced cell death. PMID: 27221474
- The data show that miRNA-mediated down-regulation of ASK1 protects mesenchymal stem cells during post-transplantation, leading to an increase in the efficacy of MSC-based cell therapy. PMID: 27775615
- Cross-talk between arginine methylation and serine phosphorylation in ASK1. PRMT5 is an ASK1-binding protein. PRMT5 mediates arginine methylation of ASK1. PMID: 26912789
- Results suggest that baicalein-mediated ASK1/JNK activation regulates the mitochondria-dependent apoptosis pathway through the up-regulation of TAp63 and down-regulation of NF-kappaB and CD74/CD44 in B-cell malignancies. PMID: 26694167
- Curcumin and ABT-737 on HCC cells were investigated for the first time, to the best of our knowledge. It was found that curcumin markedly enhanced the antitumor effects of ABT-737 on HepG2 cells and activates the ROS-ASK1-c-Jun N-terminal kinase pathway. PMID: 26707143
- ASK1 signaling regulates brown and beige adipocyte function. PMID: 27045525
- These results implicate the TNF/TRAF2/ASK1/p38 kinase pathway in modulating the risk of pulmonary complications. PMID: 26165383
- The present findings thus support our notion that ROR1 sustains lung adenocarcinoma survival, at least in part, through direct physical interaction with ASK1. PMID: 26661061
- Together, we suggest that 4SC-202 activates the ASK1-dependent mitochondrial apoptosis pathway to potently inhibit human HCC cells. PMID: 26773495
- Data show that the MAPKKK6 ASK2, a modulator of MAPKKK5 ASK1 signaling, was essential for ASK1-dependent apoptosis, but not for inducing interferon-beta (IFNB) expression. PMID: 26243192
- The expression of ASK1 is correlated with the level of claudin-6 in cervical carcinoma cells and tissues. PMID: 26191261
- ASK1 stabilizes APOBEC3G and binds HIV-1 Vif, disrupting the assemble of the Vif-ubiquitin ligase complex, thus restoring the antiviral activity of APOBEC3g. PMID: 25901786
- Data indicate that ASK1 expression is regulated by MiR-19a by targeting specific sites in the 3' untranslated region of its mRNA. PMID: 25982447
- Findings suggest that methyl isocyanate inhibits angiogenesis by inducing mitogen-activated protein kinase kinase kinase 5 ASK1-JNK-dependent endothelial cell death. PMID: 25068797
- TNF-alpha-induced ASK1-p38/JNK pathway is an important mediator of cytokine synthesis and enhanced expression of adhesion molecules in rheumatoid arthritis and is inhibited by thymoquinone. PMID: 26134265
- Cyclophilin A regulates JNK/p38-MAPK signaling through its physical interaction with ASK1. PMID: 26095851
- Knockdown of IRE1alpha by siRNA dramatically abrogated CXC195-induced activation of TRAF2, ASK and JNK, formation of an IRE1alpha-TRAF2-ASK1 complex and caspase- and mitochondrial-dependent apoptosis in T24 cells. PMID: 25797626
- Because the phosphorylation site mutants of NR4A2 cannot rescue the cell death-promoting activity, ASK1-p38 pathway-dependent phosphorylation and subsequent cytoplasmic translocation of NR4A2 may be required for oxidative stress-induced cell death. PMID: 25752609
- Collectively, these data reveal that activation of the PI3K/Akt pathway limits JNK-mediated apoptosis by phosphorylating and inactivating ASK1 during human enterovirus 71 infection. PMID: 25116390
- Siah1 is a substrate of ASK1 for activation of the GAPDH-Siah1 oxidative stress signaling cascade. PMID: 25391652
- TNF-signaling dependence of ASK1-mediated apoptosis in melanoma cells. PMID: 24574456
- Data show that ASK1 is critical for IFN gamma-induced DAPK1 via ATF6 recruitment. PMID: 25135476
- Apoptosis signal-regulating kinase 1 has a role in chondrosarcoma cell apoptosis along with endoplasmic reticulum stress due to FPipTB. PMID: 21594902
- Data suggest that degradation of ASK1 mediated by Roquin-2 is an evolutionarily conserved mechanism required for the appropriate regulation of stress responses, including pathogen resistance and cell death. PMID: 24448648
- It is activated in response to various stresses, such as reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress, and plays pivotal roles in a wide variety of cellular responses, including cell death, differentiation, and inflammation. (review) PMID: 24912301
- Data indicate that the ASK1-FoxO3a-TRADD-caspase 8 pathway is present in neural tube defects (NTDs)-affected tissues. PMID: 23982205
- MAP3K5 R256C mutation revealed attenuation of MKK4 activation through increased binding of the inhibitory protein thioredoxin (TXN/TRX-1/Trx), resulting in increased proliferation and anchorage-independent growth of melanoma cells. PMID: 24008424
- Identification of the domain through which HIV-1 Nef interacts with ASK1 and inhibits its function. PMID: 23799149
- In gastric epithelial cells, H. pylori activates ASK1 in a reactive oxygen species- and cag pathogenicity island-dependent manner, and ASK1 regulates sustained JNK activation and apoptosis induced by H. pylori. PMID: 24082073
Database Links
Protein Families
Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
Subcellular Location
Cytoplasm. Endoplasmic reticulum. Note=Interaction with 14-3-3 proteins alters the distribution of MAP3K5/ASK1 and restricts it to the perinuclear endoplasmic reticulum region.
Tissue Specificity
Abundantly expressed in heart and pancreas.
Q&A
Basic Research Questions
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What is MAP3K5 (Ab-83) Antibody and what cellular pathway does it help investigate?
MAP3K5 (Ab-83) Antibody is a phospho-specific antibody that detects MAP3K5 (also known as ASK1, Apoptosis Signal-regulating Kinase 1) only when phosphorylated at serine 83. MAP3K5/ASK1 is a serine/threonine protein kinase that plays critical roles in stress response signaling and apoptosis. This antibody enables researchers to specifically investigate the phosphorylation status at the S83 site, which is important for regulating MAP3K5's activity within the stress-activated MAPK cascade.
MAP3K5/ASK1 functions as an essential component of the MAP kinase signal transduction pathway, where it mediates cellular responses to environmental changes and stress stimuli. It phosphorylates and activates MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6, and MAP2K7/MKK7, which in turn activate JNK and p38 MAPK pathways involved in cell fate determination .
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What research applications is MAP3K5 (Ab-83) Antibody validated for?
Based on the technical documentation across multiple suppliers, MAP3K5 (Ab-83) Antibody has been validated for the following applications:
Application Recommended Dilution Validated Status Western Blot (WB) 1:500-1:2000 Validated Immunohistochemistry (IHC-P) 1:50-1:200 Validated ELISA 1:4000 Validated Immunofluorescence (IF) 1:100-1:200 Validated Proximity Ligation Assay As directed Validated The antibody has been confirmed to react with human samples, with some products also showing reactivity with mouse samples . Always perform optimization experiments to determine the optimal working dilution for your specific experimental conditions .
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How does the phosphorylation status at S83 affect MAP3K5/ASK1 function?
Phosphorylation at serine 83 (S83) represents an important regulatory mechanism for MAP3K5/ASK1 activity. Research indicates that S83 phosphorylation acts as a negative regulatory modification that can attenuate the pro-apoptotic activity of MAP3K5. When phosphorylated at this site, MAP3K5 shows decreased ability to activate downstream targets like MKK4/7 and p38, which reduces its apoptosis-inducing capacity.
This phosphorylation site appears to be mechanistically different from the activating phosphorylation at Thr845, which is required for MAP3K5's pro-apoptotic signaling. Studies have demonstrated that MAP3K5 phosphorylation state serves as a marker for its pro-apoptotic effect, with different phosphorylation sites having opposing effects on its activity .
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What is the recommended protocol for sample preparation when using MAP3K5 (Ab-83) Antibody?
For optimal results with MAP3K5 (Ab-83) Antibody, follow these sample preparation guidelines:
For Western Blotting:
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Lyse cells in buffer containing phosphatase inhibitors to preserve phosphorylation states
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Use freshly prepared samples when possible
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Denature proteins at 95-100°C for 5 minutes in sample buffer containing SDS and reducing agent
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Load 20-50 μg of total protein per lane
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Transfer to PVDF or nitrocellulose membrane
For Immunohistochemistry:
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Fix tissues in 10% neutral buffered formalin
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Embed in paraffin and section at 4-6 μm thickness
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Perform antigen retrieval (citrate buffer pH 6.0 recommended)
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Block endogenous peroxidase activity with 3% H₂O₂
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Use protein blocking solution to reduce background
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Dilute antibody in antibody diluent (1:50-1:200)
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Incubate overnight at 4°C
Always include positive controls (such as HeLa cell lysates or human lung adenocarcinoma tissue sections), which have been validated with this antibody .
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