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  4. Phospho-MLKL (S358) Recombinant Monoclonal Antibody

Phospho-MLKL (S358) Recombinant Monoclonal Antibody

  • 货号：
    CSB-RA850851A358phHU
  • 规格：
    ￥1320
  • 图片：
    • IHC image of CSB-RA850851A358phHU diluted at 1:100 and staining in paraffin-embedded human melanoma cancer performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4℃ overnight. The primary is detected by a biotinylated secondary antibody and visualized using an HRP conjugated SP system.
  • 其他：

产品详情

  • 产品描述：

    CUSABIO cloned MLKL antibody-coding genes into plasma vectors and then transfected these vector clones into mammalian cells using a lipid-based transfection reagent. Following transient expression, the recombinant antibodies against MLKL were harvested and characterized. The recombinant MLKL antibody was purified by affinity-chromatography from the culture medium. It can be used to detect MLKL protein from Human in the ELISA, IHC.

    MLKL belongs to the protein kinase superfamily. The encoded protein contains a protein kinase-like domain. It is considered inactive because it lacks several residues required for activity. Diseases associated with MLKL include young adulthood diabetes and inflammatory bowel disease. Its related pathways include DNA damage response and regulation of c-FLIP. According to some studies, MLKL may have the following characteristics.
    MLKL is a functional RIP3 substrate that binds to RIP3 through its kinase-like structure, but lacks kinase activity itself. RIP3 phosphorylates MLKL at T357 and S358. Modification of MLKL is critical for dissemination of the necrotic pathway downstream of RIPK3. Plasma membrane transport of trimeric MLKL protein is required for TNF-induced necrosis. In the absence of MLKL, RIPK3 promotes cell death and activation of the NLRP3 inflammasome. MLKL plays an important role in the necrosis of macrophages and MEFs.

  • Uniprot No.：
    Q8NB16
  • 基因名：
  • 别名：
    9130019I15Rik antibody; FLJ34389 antibody; hMLKL antibody; Mixed lineage kinase domain like antibody; Mixed lineage kinase domain like protein antibody; Mixed lineage kinase domain like pseudokinase antibody; Mixed lineage kinase domain-like protein antibody; Mlkl antibody; MLKL_HUMAN antibody
  • 反应种属：
    Human
  • 免疫原：
    A synthesized peptide derived from Human Phospho-MLKL (S358)
  • 免疫原种属：
    Homo sapiens (Human)
  • 标记方式：
    Non-conjugated
  • 克隆类型：
    Monoclonal
  • 抗体亚型：
    Rabbit IgG
  • 纯化方式：
    Affinity-chromatography
  • 克隆号：
    4A6
  • 浓度：
    It differs from different batches. Please contact us to confirm it.
  • 保存缓冲液：
    Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
  • 产品提供形式：
    Liquid
  • 应用范围：
    ELISA, IHC
  • 推荐稀释比：
    Application Recommended Dilution
    IHC 1:50-1:200
  • Protocols：
  • 储存条件：
    Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.
  • 货期：
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.

产品评价

靶点详情

  • 功能：
    Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process. Does not have protein kinase activity. Activated following phosphorylation by RIPK3, leading to homotrimerization, localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage. In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following activation by ZBP1, MLKL is phosphorylated by RIPK3 in the nucleus, triggering disruption of the nuclear envelope and leakage of cellular DNA into the cytosol.following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol. Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function.
  • 基因功能参考文献：
    1. Following activation, toggling within the MLKL pseudokinase domain promotes 4HB domain disengagement from the pseudokinase domain alphaC helix and pseudocatalytic loop, to enable formation of a necroptosis-inducing tetramer. PMID: 29930286
    2. Data show that phosphatidylinositol transfer protein alpha (PITPalpha) is involved in the function of mixed lineage kinase domain-like protein (MLKL) in necroptosis. PMID: 29104146
    3. MLKL expression alters APP metabolism and loss-of-function mutation might contribute to late-onset ApoE varepsilon4-negative AD in the Hong Kong Chinese population. PMID: 29656768
    4. Results demonstrate that MLKL concentrations measured after three days of ICU treatment in critically ill patients predict prognosis during intensive care unit treatment. These data not only suggest a previously unrecognized function of MLKL as a biomarker in critical illness and sepsis but also highlight the clinical relevance of MLKL in the pathophysiology of inflammatory and infectious diseases. PMID: 29606984
    5. Thus, activation of MLKL determines cell lysis with release of proinflammatory mediators. We found that pMLKL, the activated form of MLKL, is significantly increased in intestinal epithelial cells expressing RIP3 as well as in bioptic inflamed ileal and colonic tissues from CD and UC patients. PMID: 28844856
    6. Biological events and molecular signaling following MLKL activation during necroptosis have been reported. PMID: 28854080
    7. Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival in all patient-group with resected colon cancer. PMID: 27432118
    8. Phosphorylated MLKL leads to a conformational change, exposure of the N-terminal domain, results in MLKL membrane localization, oligomerization and membrane permeabilization. PMID: 26868910
    9. adhesion-induced eosinophil cytolysis takes place through RIPK3-MLKL-dependent necroptosis, which can be counterregulated by autophagy PMID: 28412393
    10. MLKL forms cation channels that are permeable preferentially to Mg(2+) rather than Ca(2+) in the presence of Na(+) and K(+). PMID: 27033670
    11. RIPK3 is a key factor in protection against OLs death and abnormal myelin development via its interaction with MLKL. PMID: 28230861
    12. these findings demonstrate that Trx1 is a critical regulator of necroptosis that suppresses cell death by maintaining MLKL in a reduced inactive state. PMID: 28878015
    13. this study shows that release of phosphorylated MLKL within extracellular vesicles serves as a mechanism for self-restricting the necroptotic activity of this protein PMID: 28666573
    14. this study shows that MLKL is an endogenous activator of the NLRP3 inflammasome, and that MLKL activation provides a mechanism for concurrent processing and release of IL-1beta independently of gasdermin-D PMID: 28130493
    15. Data suggest that necroptotic cells externalize phosphatidylserine (PS) after translocation of phosphorylated MLKL to cell membrane; necroptotic cells with exposed PS release extracellular vesicles containing MLKL; inhibition of MLKL after PS exposure can reverse process of necroptosis and restore cell viability. PMID: 28650960
    16. results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases. PMID: 27756058
    17. MLKL octamer formation depends on alpha-helices 4 and 5. PMID: 27920255
    18. Necroptosis signaling is modulated by the kinase RIPK1 and requires the kinase RIPK3 and the pseudokinase MLKL. (Review) PMID: 26865533
    19. In AML, MLKL expression is reduced in specific subsets. This is linked to its function in activating the ASC inflammasome. PMID: 27411587
    20. Downregulated expression of MLKL is associated with gastric caner. PMID: 27473085
    21. Results from interaction proteomics identified MLKL as a novel HSP90 client protein in HT-29 cells. PMID: 26933192
    22. coexpression of Hsp90 increases MLKL oligomerization and plasma membrane translocation and enhances MLKL-mediated necroptosis. Findings demonstrate that an efficient necrotic response requires a functional Hsp90. PMID: 26866270
    23. MLKL was a prognostic biomarker for cervical squamous cell carcinoma PMID: 26823841
    24. Modelling predicts that a C-terminal helix constrains the activity of MLKL1, but not MLKL2 PMID: 26704887
    25. Results show that upon activation, MLKL undergoes oligomerization mediated by the brace domain, being recruited to the plasma membrane through avidity of N-terminal helix bundle for phosphatidylinositol phosphate (PIP). PMID: 26853145
    26. MLKL structure determined by nuclear magnetic resonance spectroscopy reveals how different structural elements of the MLKL N-terminal region contribute to MLKL function and membrane permeation. PMID: 25220470
    27. MLKL upregulation in SPARC overexpressed cells treated with Ara-C, indicates necrosis as a possible cell death process for the SKM-1 cells under these stringent conditions PMID: 26165695
    28. in the absence of caspase-8 activity, 24(S)-Hydroxycholesterol induces a necroptosis-like cell death which is RIPK1-dependent but MLKL-independent. PMID: 25697054
    29. These data reveal a potential role for RIPK3 as a suppressor of MLKL activation and indicate that phosphorylation can fine-tune the ability of MLKL to induce necroptosis. PMID: 26283547
    30. a novel non-enzymatic function of AChE-R is to stimulate RIPK1/MLKL-dependent regulated necrosis (necroptosis). The latter complements a cholinergic system in the ovary, which determines life and death of ovarian cells. PMID: 25766324
    31. High expression of RIP3 in keratinocytes from toxic epidermal necrolysis patients potentiates MLKL phosphorylation/activation and necrotic cell death. PMID: 25748555
    32. s demonstrate that the full four-helical bundle domain (4HBD) in the N-terminal region of MLKL is required and sufficient to induce its oligomerization and trigger cell death. PMID: 24813885
    33. MLKL binding to phosphatidylinositol phosphates is required for plasma membrane rupture PMID: 24813885
    34. Report role of MLKL/RIP3 pathway in necrotic membrane disruption. PMID: 24703947
    35. MLKL protein expression is significantly upregulated in children, diagnosed with inflammatory bowel disease. PMID: 24322838
    36. Data suggest that nucleotide- (ATP-) binding residues of human MLKL have divergently evolved from mouse Mlkl and conventional protein kinases; studies include small-angle X-ray scattering, thermal shift of nucleotide binding, and sequence alignment. PMID: 24219132
    37. This study reveals a crucial mechanism of MLKL-mediated TNF-induced necroptosis. PMID: 24316671
    38. Low expression of MLKL is associated with decreased OS in patients with resected PAC and decreased RFS and OS in the subset of patients with resected PAC who receive adjuvant chemotherapy. PMID: 23720157
    39. the importance of the RIP3-MLKL interaction in the formation of functional necrosomes and suggest that translocation of necrosomes to mitochondria-associated membranes is essential for necroptosis signaling. PMID: 23612963
    40. study suggests that MLKL is a key RIP3 downstream component of TNF-induced necrotic cell death PMID: 22421439
    41. Findings implicate MLKL as a key mediator of necrosis signaling downstream of the kinase RIP3. PMID: 22265413

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  • 亚细胞定位：
    Cytoplasm. Cell membrane. Nucleus.
  • 蛋白家族：
    Protein kinase superfamily
  • 数据库链接：

    HGNC: 26617

    OMIM: 615153

    KEGG: hsa:197259

    STRING: 9606.ENSP00000308351

    UniGene: Hs.119878