Phospho-MAP3K7 (Thr184) Antibody
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Description
Structure and Function of MAP3K7/TAK1
MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7) is a serine/threonine kinase that mediates signaling downstream of multiple stimuli, including TGF-β, BMP, IL-1, and TNF . Its activation involves phosphorylation at key residues (Thr178, Thr184, Thr187, Ser192), with Thr184 being a critical site for autophosphorylation and subsequent activation of downstream kinases such as IKK-β . The Phospho-MAP3K7 (Thr184) Antibody specifically recognizes this phosphorylated state, enabling researchers to monitor TAK1 activation in various pathological contexts .
Applications in Research
The antibody is widely used in the following experimental workflows:
Role in Signaling Pathways
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Inflammation and Immunity: TAK1 phosphorylation at Thr184 is essential for NF-κB activation in response to IL-1, TNF, and TLR ligands . The antibody has been used to study TAK1’s role in chronic inflammation and autoimmune diseases .
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Cancer Biology: TAK1 activation via Thr184 phosphorylation promotes survival signaling in cancer cells, with inhibition linked to reduced tumor growth .
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Stress Response: TAK1 phosphorylates JNK and p38 kinases in response to osmotic stress, as demonstrated using this antibody .
Therapeutic Implications
Product Specs
Form
Rabbit IgG in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM 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 purchase method or location. For specific delivery details, please consult your local distributors.
Synonyms
M3K7_HUMAN antibody; MAP3K 7 antibody; Map3k7 antibody; MEKK7 antibody; Mitogen activated protein kinase kinase kinase 7 antibody; Mitogen-activated protein kinase kinase kinase 7 antibody; TAK1 antibody; TGF beta activated kinase 1 antibody; TGF-beta-activated kinase 1 antibody; TGF1a antibody; Transforming growth factor beta activated kinase 1 antibody; Transforming growth factor-beta-activated kinase 1 antibody
Target Names
Uniprot No.
Target Background
Function
MAP3K7 (also known as TAK1) is a serine/threonine kinase that plays a crucial role in the MAP kinase signal transduction pathway. It is essential for mediating cellular responses to environmental changes. TAK1 acts as a signal transducer for various stimuli, including TRAF6, cytokines (e.g., interleukin-1, transforming growth factor-beta), TGFβ-related factors (e.g., BMP2, BMP4), toll-like receptors, tumor necrosis factor receptor CD40, and B-cell receptor. Ceramides can also activate MAP3K7/TAK1. Upon activation, TAK1 functions as an upstream activator of the MKK/JNK and p38 MAPK signal transduction cascades. It achieves this by phosphorylating and activating MAP kinase kinases (MAP2Ks) like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6, and MAP2K7/MKK7. These MAP2Ks, in turn, activate p38 MAPKs, c-jun N-terminal kinases (JNKs), and I-kappa-B kinase complex (IKK). The p38 MAPK and JNK pathways regulate the transcription factor activator protein-1 (AP-1), while IKK activates nuclear factor-kappa B. MAP3K7 also activates IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, TAK1 plays a crucial role in activating MAPK8/JNK1 but not NF-kappa-B. It also promotes TRIM5 capsid-specific restriction activity. TAK1 phosphorylates RIPK1 at 'Ser-321,' positively regulating RIPK1 interaction with RIPK3 to promote necroptosis. However, it negatively regulates RIPK1 kinase activity and its interaction with FADD, thus inhibiting apoptosis.
Gene References Into Functions
- A novel splicing variant in MAP3K7 was identified in a patient exhibiting features of cardiospondylocarpofacial syndrome and hereditary connective tissue disorder. PMID: 29467388
- TAK1 plays a critical role in facilitating the adaptation of triple-negative breast cancer cells to the lung microenvironment by promoting positive feedback signaling through P38. PMID: 29777109
- TAK1 can function as a direct upstream kinase for AMPK in specific contexts and in response to certain activating stimuli. Further research is needed to elucidate the precise signaling mechanisms that regulate TAK1-mediated phosphorylation and activation of AMPKalpha at T172. [review] PMID: 30111748
- IL-17F significantly induced the expression of IL-6 gene and protein. IL-17F activated TAK1 and NF-kappaB in airway smooth muscle cells. PMID: 28474507
- Overexpression of miR-20a reduced colony formation and tumor growth in osteosarcoma cells. This effect was likely mediated by targeting TAK1 expression. Notably, miR-20a overexpression sensitized osteosarcoma cells to chemotherapeutic drugs. PMID: 29327611
- TGFbeta and IL1beta signaling interact at the SMAD2/3 level in human primary MSCs. IL1beta repressed downstream TGFbeta target genes independent of C-terminal SMAD2 phosphorylation. Our study demonstrates that SMAD2/3 linker modifications are crucial for this interplay and identifies TAK1 as a key mediator of IL1beta-induced TGFbeta signal modulation. PMID: 28943409
- Increased TAK1 expression may contribute to the progression of gastric cancer. PMID: 28714004
- miR-146a, functioning as a tumor suppressor, significantly promotes GC cell apoptosis by inhibiting the NF-kappaB signaling pathway through targeting TAK1. PMID: 28560435
- Our findings demonstrate that TRADD, TRAF2, RIP1, and TAK1 play a role in regulating TNF-alpha signaling in human myometrium. These findings are significant considering the central role of TNF-alpha in human labor and delivery. PMID: 28337828
- Rab1 is regulated by the host in a similar manner. Innate immunity kinase TAK1 and Legionella effectors compete to regulate Rab1 through switch II modifications during infection. PMID: 27482120
- nMet accelerated HCC tumorigenesis and metastasis by activating the TAK1/NF-kappaB pathway. PMID: 28989054
- TAK1 protein expression was elevated in cartilage tissue from spinal tuberculosis patients. PMID: 28829887
- TAK1 regulates Nrf2 by modulating Keap-p62/SQSTM1 interaction. This regulation is essential for maintaining antioxidant protection in the intestinal epithelium. PMID: 27245349
- Overexpression of TAK1 was strongly associated with positive lymph node metastasis in pancreatic ductal adenocarcinoma. PMID: 28194669
- Dysregulation of the TAK1 complex produces a phenotype closely resembling Frontometaphyseal Dysplasia caused by FLNA mutations. Furthermore, the pathogenesis of some filaminopathies caused by FLNA mutations might be mediated by misregulation of signaling coordinated through the TAK1 signaling complex. PMID: 27426733
- Although TAK1 is involved in inflammation, immunity, and cancer, this study reports MAP3K7 mutations in a developmental disorder primarily affecting cartilage, bone, and heart. PMID: 27426734
- This study suggests that aberrant TAK1 activity impairs autophagy, leading to alterations in the vitality of retinal pigment epithelial cells. PMID: 26928052
- TAK1 may be an important factor in the pathogenesis of thyroid cancer, and targeted down-regulation of TAK1 might improve the prognosis of patients with thyroid cancer. PMID: 26823762
- Loss of MAP3K7 is associated with esophageal squamous cell carcinoma. PMID: 26406417
- This study highlights that targeting the BMP and TGFbeta type I and type II receptors causes a downregulation of XIAP, TAK1, and Id1, leading to cell death in lung cancer cells. PMID: 27048361
- Polyubiquitination of Transforming Growth Factor beta-activated Kinase 1 (TAK1) at Lysine 562 Residue Regulates TLR4-mediated JNK and p38 MAPK Activation. PMID: 26189595
- The data emphasize the central role of TAK1 in controlling signaling cascades and functional responses in primary neutrophils, making it a promising target for therapeutic intervention in view of the role of neutrophils in chronic inflammatory conditions. PMID: 26491199
- MiR-377 is a significant negative regulator of E2F and MAP3K7/NF-kB signaling pathway in melanoma cells. PMID: 25889255
- Findings indicate that the TAK1 signaling pathway may be a suitable target for designing new antifibrotic therapies. PMID: 26185333
- Data indicate that SHIP2 is a regulator of lymphatic function in humans, and inherited mutations in the INPPL1 gene may act in concert with HGF and likely MAP3K7 mutations to exacerbate lymphatic phenotypes. PMID: 25383712
- Data suggest that inhibition of TGF-beta-activated protein kinase 1 (TAK1) reduces chemokine (C-C motif) receptor 7 (CCR7) expression. PMID: 25557171
- This study identifies coordinate loss of MAP3K7 and CHD1 as a unique driver of aggressive prostate cancer development. PMID: 25770290
- Data indicate 4-substituted 1H-pyrrolo[2,3-b]pyridines as potent inhibitors against TGFbeta-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2). PMID: 25075558
- Ubc13 was dispensable for transforming growth factor beta (TGFbeta)-induced SMAD activation but was required for activation of non-SMAD signaling via TGFbeta-activating kinase 1 (TAK1) and p38. PMID: 25189770
- Data show that the ECSIT (evolutionarily conserved signaling intermediate in Toll pathways) complex, including MEKK7 (TAK1) and TNF receptor-associated factor 6 (TRAF6), plays a role in Toll-like receptor 4 -mediated signals to activate NF-kappa B. PMID: 25371197
- Data suggest a role for the mitogen-activated protein kinase kinase kinase 7 TAK1-jun-NH2-Terminal Kinase JNK pathway as a critical regulator of NLRP3 protein inflammasome activation. PMID: 25288801
- Nef markedly activated TAK1 in M-CSF-derived M2-MPhi but not in GM-CSF-derived M1-MPhi. PMID: 24874739
- TAK1 may be an important oncogene or an effective target for renal cell carcinoma intervention. PMID: 25261726
- TAK1 plays a role in tumor initiation, progression, and metastasis as a tumor prompter or tumor suppressor. A comprehensive understanding of the role of TAK1 in liver physiology and diseases is crucial for developing therapeutic agents targeting TAK1. PMID: 24443058
- Data suggest that TAK1 and IKKbeta (inhibitor of kappaB kinase beta) phosphorylate different serines of IKKbeta; TAK1-catalyzed phosphorylation of IKKbeta at Ser177 is a priming event that enables IKKbeta to activate itself by phosphorylating Ser181. PMID: 24911653
- NLK functions as a pivotal negative regulator of NF-kappaB by disrupting the interaction of TAK1 with IKKbeta. PMID: 24721172
- Data indicate that ribosomal S6 kinase 1 (S6K1) is negatively involved in the toll-like receptorS TLR2 and TLR4 signaling pathway by inhibiting TAK1 (MAP3K7) activity. PMID: 24277938
- A dysregulated balance in the activation of TGFbeta-TAK1 and TGFbeta-SMAD pathways is pivotal for TGFbeta1-induced epithelial-mesenchymal transition. PMID: 24113182
- Overexpression of TAK1 predicts a poor prognosis in patients with clear cell renal cell carcinoma, suggesting that TAK1 may serve as a novel prognostic marker. PMID: 23534745
- Our study identifies MAP3K7 deletion as a prominent feature in ERG-negative prostate cancer. PMID: 23370768
- Results establish TAK1 as an AMPKalpha1 kinase that regulates vascular endothelial growth factor-induced and cytokine-induced angiogenesis by modulating SOD2 expression and the superoxide anion:hydrogen peroxide balance. PMID: 24072697
- TAK1 (MAP3K7) does not mediate the TGFb-induced phosphorylation of p38 mitogen-activated protein kinases. PMID: 23760366
- 14-3-3epsilon associates with TAK1 in a phosphorylation-dependent manner to determine the cell fate of Bleomycin-treated HCC cells. PMID: 23472066
- Two SNPs, rs282070 located in intron 1 of the MAP3K7 gene and rs2111699 located in intron 1 of the GSTZ1 gene, were significantly associated (after adjustment for multiple testing) with longevity in stage 2. PMID: 22576335
- Results indicate that TAK1 and p38 kinases appear to be central in the 'priming effect' of LTB(4) on neutrophils to enhance response to Toll-like receptor ligands. PMID: 22843747
- Findings suggest that DUSP14 negatively regulates TNF- or IL-1-induced NF-kappaB activation by dephosphorylating TAK1 at Thr-187. PMID: 23229544
- TAK1 expression correlates with lymph node metastasis and is a negative, independent prognostic factor in resected T3N1-3M0 ESCCs. PMID: 23272845
- TAK1 plays a central role in both innate and adaptive immunity, as well as in DNA damage, osmotic stress, and hypoxia. (Review) PMID: 22941947
- We found that endothelial TAK1 and TAB2, but not TAB1, were critically involved in vascular formation. PMID: 22972987
- This review focuses on current insights into the mechanism and function of the Smad-independent signaling pathway via TGF-beta-activated kinase 1 and its role in mediating the profibrotic effects of TGF-beta1 in chronic kidney disease. [Review Article] PMID: 22835455
Database Links
Involvement In Disease
Frontometaphyseal dysplasia 2 (FMD2); Cardiospondylocarpofacial syndrome (CSCF)
Protein Families
Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
Subcellular Location
Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=Although the majority of MAP3K7/TAK1 is found in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2, it is also localized at the cell membrane.
Tissue Specificity
Isoform 1A is the most abundant in ovary, skeletal muscle, spleen and blood mononuclear cells. Isoform 1B is highly expressed in brain, kidney and small intestine. Isoform 1C is the major form in prostate. Isoform 1D is the less abundant form.
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