Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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mitogen-activated protein kinase kinase kinase 7(MAP3K7) mitogen-activated protein kinase kinase kinase 7(MAP3K7) Related Genes Homo sapiens
CYTOBAND 6q16.1-q16.3,
GENERIF_SUMMARY Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol., TAK1-dependent activation of AP-1 and c-Jun N-terminal kinase by receptor activator of NF-kappaB., The TAK1-TAB1 fusion protein is a novel constitutively active mitogen-activated protein kinase kinase kinase that stimulates AP-1 and NF-kappaB signaling pathways, TNFalpha activation of the NF-kappaB pathway is associated with the inducible binding of TAK1 to TRAF2 and both IKKalpha and IKKbeta, TAK1- and MKK3-mediated activation of p38 are facilitated by Smad7, Pellino2 interacts with TAK1 and activates the MAP kinase pathway., TAK1 has a role in TNF-alpha induced IKK phosphorylation of NF-kappaB p65, Results indicate that dominant negative constructs of TAK1 retain the ability to intercept the TGF-beta signaling effectively., TAB1 participates in a SAPK2a/p38alpha-mediated feedback control of TAK1, Tak1 has a role in Wnt signal transduction and phosphorylation and inhibition of TCF, TAK1 protein kinase mediate IKK activation by BCL10 and MALT1. RNAi-mediated silencing of TAK1 suppressed TCR-dependent IKK activation and interleukin-2 production in T cells, TAK1 binds with Sef, which has a role in JNK activation and apoptosis, characterized the molecular mechanisms of cellular stress-induced TAK1 activation, focusing mainly on the phosphorylation of TAK1 at Thr-187 and Ser-192 in the activation loop; TAB1 and TAB2 were differentially involved in the phosphorylation of TAK1, Experiments using dominant-negative Tpl2 suggest this kinase functions distal to TRAFs but proximal to the TAK1/TAB1 signaling complex, within the IKK/NFkappaB activation pathway., STAT3 enhances the efficiency of its own Ser-727 phosphorylation by acting as a scaffold for the TAK1-NLK kinases, interleukin-1beta and its downstream mediator TAK1 inhibit mothers against decapentaplegic homolog 3 MAD-mediated TGFbeta target gene activation, Arachidonic acid-mediated TAK1 activation is responsible for MAP kinase kinase 6 activation and the ensuing downstream signaling in metastatic human breast carcinoma cells, Involvement of the TAB2/TRAF6/TAK1 signalling complex in the Edar signal transduction pathway has important implications for understanding of NF-kappaB activation and anhidrotic ectodermal dysplasia in human., TAK1 is recruited to the TNF-R1 complex via RIP and likely cooperates with MEKK3 to activate NF-kappaB in TNF-alpha signaling, LMP1 utilizes two distinct pathways to activate NF-kappaB, TAK1 plays a critical role in T cell activation by controlling production of IL-2., an LMP1-associated complex containing TRAF6, TAB2, and TAK1 plays an essential role in the activation of JNK, A candidate gene in ectodermal dysplasia., TAK1 is a functional member of the Snf1/AMPK kinase family, the TAK1-JNK pathway is activated by osmotic stress, while blocking TAK1-mediated NF-kappaB activation; TAO2 regulates TAK1 pathways, the nuclear factor-kappaB signaling pathway is inhibed by gamma-tocopherol through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and potentiation of apoptosis, The TAB2/TAB3 interaction with TAK1 is crucial for the activation of signaling cascades mediated by interleukin-1, tumor necrosis factor, and receptor activator of nuclear factor-kappa B ligand (RANKL)., HspB8 overload causes melanoma growth arrest and apoptosis through TAK1 activation, HSP27 is required for both IL-1 and TNF-induced signaling pathways for which the most upstream common signaling protein is TAK1., Modulates TGF-beta-dependent cellular responses by targeting SnoN/SKIL for degradation, thereby allowing the activation of TGF-beta target genes., TAK1 is thought to play a causative role in the determination of a finite replicative lifespan of normal and cancer cells, Study shows that Tax functions as an intracellular stimulator of an IKK-activating kinase, Tak1; in addition, Tax physically interacts with Tak1 and mediates the recruitment of IKK to Tak1., IHPK2-TRAF2 binding leads to attenuation of TAK1- and NF-kappaB-mediated signaling and is partially responsible for the apoptotic activity of IHPK2., TAK1 as a pivotal upstream kinase and potential therapeutic target to modulate synoviocyte activation in RA., BY acting at the level of TAK1 (MAP3K7) activation, YopJ inhibited TLR-mediated NF-kappaB and MAP kinase activation as well as IRF3 signalling., p38 negatively regulated TAK1 activity through TAB1 phosphorylation., TAK1 contributes to TGF-beta1-mediated tumor angiogenesis and metastasis via involvement of the TAK1-NF-kappaB-MMP-9 pathway., These signals exert their anti-inflammatory effects by inhibiting phosphorylation of TAK1, two independent and indispensable signaling pathways-1) JAK1-associated PI3K signaling and 2) Act1/TRAF6/TAK1-mediated NF-kappaB activation-are stimulated by IL-17A to regulate gene induction in human airway epithelial cells., Data provide insights into the homeostatic interactions that maintain basal NF-kappaB levels by holding the enzymes MEKK3 and TAK1 in their inactive state., PP2A functions as a negative regulator in TGF-beta1-induced TAK1 activation, a TAB1, suggest that Pellino 3b acts as a negative regulator for IL-1 signaling by regulating IRAK degradation through its ubiquitin protein ligase activity, TAB4 binds TAK1 and polyubiquitin chains to promote specific sites of phosphorylation in TAK1-TAB1, which activates IKK signaling to NF-kappaB., Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop is required for interleukin (IL)-1-mediated optimal NFkappaB and AP-1 activation as well as IL-6 gene expression., TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6., Hsp90 regulates IL-1beta-induced signaling by interacting with TAK1 and maintaining the stability of TAK1, suggesting that Hsp90 might act as the chaperone of TAK1 in immune and inflammatory responses related with IL-1 signal cascades., These results suggest that Hsp90 is required for the folding and stability of TAK1 but is displaced and no longer required when TAK1 is complexed to TAK1-binding protein-1., as a mediator of SF- and Src-stimulated NF-kappaB activity. Finally, the Src/Rac1/MKK3/6/p38 and Src/TAK1/NF-kappaB-inducing kinase pathways exhibited cross-talk at the level of MKK3., the presence of melittin, TRAIL-induced apoptosis is significantly increased in TRAIL-resistant HCC cells, which may be attributed to melittin-induced TAK1-JNK/p38 activation and melittin-mediated inhibition of IkappaBalpha kinase-NFkappaB., TRAIL-induced AMPK activation depends on transforming growth factor-beta-activating kinase 1 (TAK1) and TAK1-binding subunit 2., These results suggest that FBXW5 negatively regulates TAK1 in the IL-1beta signaling pathway., Data indicate that TAK1-D plays a role in the signaling events triggered by selected types of ribotoxic stress., TNFalpha and its downstream TAK1, which are key mediators for NF-kappaB and MAPK pathways, may be involved in the pathogenesis of endometriosis., novel homeostatic control of keratinocyte proliferation and migration mediated via TAK1 regulation of von Hippel-Lindau tumor suppressor, periostin is involved in the suppression of cell invasiveness via the TAB1/TAK1 signaling pathway., results indicate that unanchored polyubiquitin chains directly activate TAK1 and IKK, suggesting a new mechanism of protein kinase regulation, These results demonstrated that TAK1 controls two different signaling pathways, IkappaB kinase-NF-kappaB and MAPK-EGFR, leading to the survival of cells exposed to the death signal from the TNF-alpha receptor., polyubiquitination of TAK1 regulates the activation of NF-kappaB, which in turn is used by H. pylori CagA for the H. pylori-induced inflammatory response, Lys(63)-linked polyubiquitination of TAK1 at Lys(158) is essential for its own kinase activation and its ability to mediate its downstream signal transduction pathways in response to TNFalpha and IL-1beta stimulation., findings provide the first evidence that TAK1-NLK pathway is a novel regulator of FOXO1, Co-expression of TAK1 and TAB1 resulted in a functional and active TAK1-TAB1 complex capable of directly activating full-length heterotrimeric mammalian AMP-activated protein kinase (AMPK) in vitro., A20 improves cardiac functions and inhibits cardiac hypertrophy, inflammation, apoptosis, and fibrosis by blocking transforming growth factor-beta-activated kinase 1-dependent signaling., The systemic TAK1 gene silencing decreases the frequency of Th1 and Th17 cells, both mediating autoimmunity in experimental arthritis, demonstrating the immunomodulatory potential of TAK1., TAK1 lysine 158, but not lysine 34, is required for TGF-beta-induced TAK1 polyubiquitination and TGF-beta-induced TRAF6-mediated Smad-independent IKK, JNK and p38 activation., ATM- and NEMO-dependent ubiquitination of ELKS leads to the ubiquitin-dependent assembly of TAK1/TAB2/3 and NEMO/IKK complexes, resulting in IKK and NF-kappaB activation following genotoxic stimuli., p38 maintains E-cadherin expression by suppressing TAK1-NF-kappaB signaling, thus impeding the induction of epithelial-to-mesenchymal transition in human primary mesothelial cells., LPS-induced activation of IRAK4 and TAK1, K63-linked polyubiquitination of IRAK1 and TRAF6, and disrupted IRAK1-TRAF6 and IRAK1-IKKgamma assembly associated with increased A20 expression, The TAK1 regulated inhibition of TNF-alpha-mediated apoptosis via the autocrine action of stem cell factor., TAK1-c-Rel and IRF4 pathways play distinct roles in the maintenance of IL-9-producing Th17 phenotype of HTLV-1-transformed cells, Data show that DNA damage stimulates the formation of a cytosolic complex of ATM, NEMO, RIP1, and TAK1, and that TAK1 mediates the NF-kappaB and p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein 2 responses to DNA damage., these studies show that the TAK1-TAB2-TAB3 signaling axis is critical for carcinoma-induced bone lesions, mediating expression of proinvasive and osteolytic factors., Results that genetic silencing or inhibition of TAK1 kinase activity in vivo is a potential therapeutic approach to reversal of the intrinsic chemoresistance of pancreatic cancer., TAK1 plays a major role in growth factor-induced phenotypic modulation of airway smooth muscle remodeling., polyubiquitination of TAK1 is correlated with activation of TAK1 and is essential for activation of NF-kappaB signaling downstream of several receptors, TAK1 and its adapter protein, TAB2, reciprocally regulate both TAK1- and ASK1-mediated signaling pathways to direct the activations of NF-kappaB and AP-1., Study on effect of fushenkeli on expression of TAK1 in human renal tubular epithelial cells and its possible mechanism, data suggest that TAK1 functions as a prosurvival mediator in cancer cells displaying hyperactive KRAS-dependent Wnt signaling., TAK1 activity was required for HIV-1 gp41 cytoplasmic domain-mediated NF-kappaB activation, and HIV-1-derived gp41 cytoplasmic domain physically interacted with TAK1 through the same region required for NF-kappaB activation., Inhibition of transforming growth factor-activated kinase 1 (TAK1) blocks and reverses epithelial to mesenchymal transition of mesothelial cells, In the grafts containing Tak1-suppressed prostate stem cells, p38 and c-jun-NH(2)-kinase activity was attenuated and proliferation was increased, the role of TAK1 in cell death, cell cycle regulation and apoptosis after X irradiation is independent of NF-kappaB, p38 MAPK, and ERK phosphorylation, and dependent, in part, on p21 induction, 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, Kaposi's sarcoma associated herpesvirus encoded viral FLICE inhibitory protein K13 activates NF-kappaB pathway independent of TRAF6, TAK1 and LUBAC, The phosphorylated form of TAK1 is abundantly expressed in a panel of lymphoma cell lines, including mantle cell, anaplastic large cell, and Hodgkin lymphoma. siRNA inhibited the activation of NF-kappaB and p38 and induced apoptosis in lymphoma cell lines., evidence that TAK1 is a target for YopJ-mediated inhibition., 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], 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., TAK1 plays central role in both innate and adaptive immunity as well as in DNA damage, osmotic stress, and hypoxia. (Review), We found that endothelial TAK1 and TAB2, but not TAB1, were critically involved in vascular formation, findings suggest that DUSP14 negatively regulates TNF- or IL-1-induced NF-kappaB activation by dephosphorylating TAK1 at Thr-187, TAK1 expression correlates with lymph node metastasis and is a negative, independent prognostic factor in resected T3N1-3M0 ESCCs., our study identifies MAP3K7 deletion as a prominent feature in ERG-negative prostate cancer, 14-3-3epsilon associates with TAK1 in a phosphorylation-dependent manner to determine the cell fate of Bleomycin-treated HCC cells, Overexpression of TAK1 predicts a poor prognosis in patients with clear cell renal cell carcinoma, so that TAK1 may serve as a novel prognostic marker, TAK1 (MAP3K7) does not mediate the TGFb-induced phosphorylation of p38 mitogen-activated protein kinases., 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, A dysregulated balance in the activation of TGFbeta-TAK1 and TGFbeta-SMAD pathways is pivotal for TGFbeta1-induced epithelial-mesenchymal transition., Data indicate that ribosomal S6 kinase 1 (S6K1) is negatively involved in the toll-like receptorS TLR2 and TLR4 signaling pathway by the inhibition of TAK1 (MAP3K7) activity., TAK1 plays a role in tumor initiation, progression, and metastasis as a tumor prompter or tumor suppressor. An understanding of the role of TAK1 in liver physiology and diseases is required for the development of therapeutic agencies targeting TAK1, NLK functions as a pivotal negative regulator of NF-kappaB via disrupting the interaction of TAK1 with IKKbeta., Nef markedly activated TAK1 in M-CSF-derived M2-MPhi but not in GM-CSF-derived M1-MPhi., Data suggest TAK1 and IKKbeta (inhibitor of kappaB kinase beta) phosphorylate different serines of IKKbeta; TAK1-catalyzed phosphorylation of IKKbeta at Ser177 is priming event that enables IKKbeta to activate itself by phosphorylating Ser181., 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)., 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, TAK1 may be an important oncogene or an effective target for renal cell carcinoma intervention., 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., 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., Findings indicate that SHIP2 is a regulator of lymphatic function in humans and that inherited mutations in the INPPL1 gene may act in concert with HGF, and likely MAP3K7, mutations to exacerbate lymphatic phenotypes., Data indicate that inhibition of TGF-beta-activated protein kinase 1 (TAK1) reduces chemokine (C-C motif) receptor 7 (CCR7) expression., identify coordinate loss of MAP3K7 and CHD1 as a unique driver of aggressive prostate cancer development, MiR-377 is an important negative regulator of E2F and MAP3K7/NF-kB signaling pathway in melanoma cells., the TAK1 signaling pathway may represent a suitable target to design new, antifibrotic therapies, Polyubiquitination of Transforming Growth Factor beta-activated Kinase 1 (TAK1) at Lysine 562 Residue Regulates TLR4-mediated JNK and p38 MAPK Activation, 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., This paper 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 of lung cancer cells.,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., cofactor:Magnesium., function:Component of a protein kinase signal transduction cascade. Mediator of TGF-beta signal transduction. Stimulates NF-kappa-B activation and the p38 MAPK pathway., PTM:Association with MAP3K7IP1 promotes autophosphorylation and subsequent activation. Dephosphorylation at Thr-187 by PP2A and PPP6C leads to inactivation., similarity:Belongs to the protein kinase superfamily., similarity:Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily., similarity:Contains 1 protein kinase domain., subunit:Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with MAP3K7IP1 and MAP3K7IP2. Interacts with PPM1L. Interaction with PP2A and PPP6C leads to its' repressed activity.,