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MAP3K7 — RELA
Pathways - manually collected, often from reviews:
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Ninomiya-Tsuji et al., Nature 1999
:
Stimulation of
TAK1 causes activation of
NF-kappaB , which is blocked by dominant negative mutants of NIK, and an inactive TAK1 mutant prevents activation of NF-kappaB that is mediated by IL-1 but not by NIK
Sakurai et al., J Biol Chem 1999
:
Here we investigated the molecular mechanism of
TAK1 induced
NF-kappaB activation ... Dominant negative mutants of IkappaB kinase (IKK) alpha and IKKbeta inhibited
TAK1 induced
NF-kappaB activation
Irie et al., FEBS Lett 2000
:
A kinase negative mutant of
TAK1 inhibited the LPS induced
NF-kappaB activation both in a macrophage-like cell line, RAW 264.7, and in human embryonic kidney 293 cells expressing toll-like receptor 2 or 4
Mochida et al., Kokubyo Gakkai Zasshi 2000
(MAP Kinase Signaling System) :
Here we report that ASK 1 binds to TAK 1 and dissociates TAK 1 from TNF receptor associated factor 6 ( TRAF 6 ), and inhibits
TAK 1- and TRAF 6-, but not
NF-kappa B-inducing kinase (NIK) induced NF-kappa B
activation
Holtmann et al., J Biol Chem 2001
:
Expression of the MAP kinase kinase kinase ( MAPKKK )
TAK1 together with its coactivator TAB1 in HeLa cells activated all three pathways and was
sufficient to induce IL-8 formation,
NF-kappaB + JNK2 mediated transcription from a minimal IL-8 promoter, and p38 MAPK mediated stabilization of a reporter mRNA containing IL-8 derived regulatory mRNA sequences
Yeung et al., Mol Cell Biol 2001
:
Raf kinase inhibitor protein interacts with
NF-kappaB inducing kinase and
TAK1 and inhibits NF-kappaB activation
Mizukami et al., Mol Cell Biol 2002
(MAP Kinase Signaling System) :
Dominant negative forms of
TAK1 and TAB2
inhibit NF-kappaB activation induced by overexpression of RANK ... Furthermore, in murine monocyte RAW 264.7 cells, dominant negative forms of
TAK1 and TAB2
inhibit NF-kappaB activation induced by RANKL and endogenous TAK1 is activated in response to RANKL stimulation
Lee et al., J Biochem Mol Biol 2002
:
TAK1 dependent
activation of AP-1 and c-Jun N-terminal kinase by receptor activator of
NF-kappaB ... The inhibitory
effect of the
TAK1 mutant on RANK- and TRAF induced
NF-kappaB activation was also observed, but less efficiently
Jiang et al., J Biol Chem 2003
(MAP Kinase Signaling System) :
Kinase inactive mutants of
TAK1 ( TAK1DN ) and PKR ( PKRDN )
inhibit poly ( dI.dC ) -induced TLR3 mediated
NFkappaB activation, suggesting that both of these kinases play important roles in this pathway
Cho et al., Toxicol Lett 2003
:
The dominant negative mutant forms of
TAK1 and NIK
inhibited the silica induced
NF-kappaB activation in Rat2 cells
Silverman et al., J Biol Chem 2003
:
Immune activation of
NF-kappaB and JNK
requires Drosophila
TAK1
Chen et al., J Biol Chem 2004
(Crohn Disease) :
Nod2, acting in a reciprocal manner, inhibited
TAK1 induced
NF-kappaB activation in RICK-deficient embryonic fibroblasts ... Nod2 appears to interact with TAK1 through its LRR region to exert its inhibitory effect on
TAK1 induced
NF-kappaB activation ... Further, wild-type LRR more effectively suppressed
NF-kappaB activation
induced by
TAK1 than LRR with a 3020insC mutation
Chen et al., Biochem Biophys Res Commun 2004
:
Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via
TLR2-TAK1 dependent p38 MAPK-AP1 and
IKKbeta-IkappaBalpha-NF-kappaB signaling pathways ... Moreover, P6 induces MUC5AC transcription via
TLR2-MyD88-IRAK1-TRAF6-TAK1 dependent p38 MAPK-AP1 and
IKKbeta-IkappaBalpha-NF-kappaB signaling pathways
Rannou et al., Joint Bone Spine 2006
(Arthritis, Rheumatoid) :
When these cytokines bind to their membrane receptor, they set off signaling cascades, with
activation of TGFbeta activating kinase (
TAK-1 ), of
NF-kappaB by Ikappa-B kinase, of mitogen activated protein kinases ( MAP kinases ), and finally of activator protein-1 (AP-1)
Morlon et al., Hum Mol Genet 2005
(Ectodermal Dysplasia) :
TAB2, TRAF6 and
TAK1 are
involved in
NF-kappaB activation induced by the TNF-receptor, Edar and its adaptator Edaradd ... Moreover, we show that dominant negative forms of TAB2, TRAF6 and
TAK1 blocked the
NF-kappaB activation induced by Edaradd
Shim et al., Genes Dev 2005
:
However,
TAK1 is not
required for
NF-kappaB activation through the alternative pathway following LT-beta signaling
Wu et al., J Biol Chem 2006
(Cell Transformation, Neoplastic) :
Furthermore, we showed that
TAK1 is
required for
NF-kappaB activation by LMP1
Haase et al., J Immunol 2005
(Yersinia Infections) :
TAK1 is an important
activator of the
IkappaB kinase complex in the TLR signaling cascade
Uemura et al., J Biol Chem 2006
:
TAK1 is a component of the Epstein-Barr virus LMP1 complex and is
essential for activation of JNK but not of
NF-kappaB
Neumann et al., Biol Chem 2006
:
Furthermore, we show that mitogen activated protein kinase kinase kinases (
MAP3K ), like TPL2 ( tumour progression locus 2 ) and transforming growth factor beta activated kinase 1 ( TAK1 ), have no impact on H. pylori
induced activation of
NF-kappaB
Huang et al., Cell Death Differ 2006
:
Osteoclast differentiation
requires TAK1 and MKK6 for NFATc1 induction and
NF-kappaB transactivation by RANKL ...
TAK1-DN , MKK6-DN, and SB203580, but not MKK3-DN, also
suppressed RANKL stimulation of
NF-kappaB transcription activity in a manner dependent on p65 phosphorylation on Ser-536
Ishizawa et al., Biol Cell 2006
:
xFADD and xRIP1 synergistically
induced the activation of AP-1 and
NF-kappaB , both of which were partially mediated by TRAF2 ( tumour-necrosis-factor-receptor associated factor 2 ) and
TAK1 ( transforming-growth-factor-beta activated kinase 1 )
Sethi et al., J Biol Chem 2006
:
NF-kappaB reporter activity
induced by TNFR1, TNF receptor associated death domain, TRAF2,
TAK1 , NF-kappaB inducing kinase, and IKKbeta was inhibited by indirubin but not that induced by p65 transfection
Wan et al., Nat Immunol 2006
:
In mature thymocytes,
TAK1 was
required for interleukin 7-mediated survival and T cell receptor dependent activation of transcription factor
NF-kappaB and the kinase Jnk
Kettner-Buhrow et al., Biochem Biophys Res Commun 2006
(MAP Kinase Signaling System) :
dsiRNA against TAK1 or TAB1 significantly suppressed their target proteins as well as
TAK1 mediated
activation of
NFkappaB , p38 MAPK, and JNK, and of IL-8 transcription
Huangfu et al., J Biol Chem 2006
:
Osmotic stress activates the TAK1-JNK pathway while blocking
TAK1 mediated
NF-kappaB activation : TAO2 regulates TAK1 pathways ... Furthermore, we found that although
TAK1 was highly activated upon osmotic stress, it could not
induce degradation of IkappaB or activation of
NF-kappaB ... We found that TAO2 ( thousand-and-one amino acid kinase 2 ) associates with TAK1 and can inhibit
TAK1 mediated activation of
NF-kappaB but not of JNK
Sethi et al., Blood 2007
(Neoplasm Invasiveness...) :
Celastrol, a novel triterpene, potentiates TNF induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-kappaB regulated gene products and
TAK1 mediated
NF-kappaB activation ... Recent studies indicate that TNF induced IKK activation requires activation of TAK1, and we indeed found that celastrol inhibited the
TAK1 induced
NF-kappaB activation
Delaney et al., Cell cycle (Georgetown, Tex.) 2006
:
For example,
NFkappaB signaling in a particular cell may or may not
require TAK1 depending on the nature of the activating signal
Gohda et al., Biochem Biophys Res Commun 2007
:
These results strongly suggest that unlike cytokine signaling, Tax induced
NFkappaB activation does not
involve K63 polyubiquitination mediated
MAP3K activation
Pandey et al., J Biol Chem 2007
:
As examined by DNA binding, we found that butein suppressed tumor necrosis factor (TNF) induced NF-kappaB activation in a dose- and time dependent manner ; suppressed the NF-kappaB activation induced by various inflammatory agents and carcinogens ; and inhibited the
NF-kappaB reporter activity
induced by TNFR1, TRADD, TRAF2, NIK,
TAK1/TAB1 , and IKK-beta
Suzuki et al., J Biol Chem 2007
(Cell Transformation, Viral...) :
Constitutive activation of
TAK1 by HTLV-1 tax dependent overexpression of TAB2
induces activation of JNK-ATF2 but not
IKK-NF-kappaB ... Surprisingly,
TAK1 was not
involved in the activation of
NF-kappaB
Pandey et al., Blood 2007
(Neoplasm Metastasis) :
GA suppressed
NF-kappaB activation induced by various inflammatory agents and carcinogens and this, accompanied by the inhibition of
TAK1/TAB1 mediated IKK activation, inhibited IkappaBalpha phosphorylation and degradation, suppressed p65 phosphorylation and nuclear translocation, and finally abrogated NF-kappaB dependent reporter gene expression
Safina et al., Oncogene 2008
(Lung Neoplasms...) :
Dn-TAK1 reduces
NF-kappaB transcriptional response and inhibition of NF-kappaB reduces expression of MMP-9 and activity of the MMP-9 promoter reporter
Yang et al., J Biol Chem 2007
(Tuberculosis) :
We also demonstrate a
requirement for the E2-conjugating enzyme Ubc13, the E3 ubiquitin ligase Traf6, and the ubiquitin activated kinase
Tak1 in Nod2 mediated
NF-kappaB activation
Madhavan et al., J Immunol 2007
:
Biomechanical signals suppress
TAK1 activation to
inhibit NF-kappaB transcriptional activation in fibrochondrocytes
Huang et al., J Immunol 2007
:
Requirement for both JAK mediated PI3K signaling and
ACT1/TRAF6/TAK1 dependent
NF-kappaB activation by IL-17A in enhancing cytokine expression in human airway epithelial cells
Xiao et al., J Biol Chem 2008
:
Pellino 3b negatively regulates interleukin-1 induced
TAK1 dependent
NF kappaB activation
Tang et al., J Exp Med 2008
(Bone Marrow Diseases...) :
Activation of
TAK1 by proinflammatory cytokines and T and B cell receptors
induces the nuclear localization of
nuclear factor kappaB (NF-kappaB) and the activation of c-Jun N-terminal kinase (JNK)/AP1 and P38, which play important roles in mediating inflammation, immune responses, T and B cell activation, and epithelial cell survival
Yu et al., J Biol Chem 2008
:
Consistently,
TAK1 mutant with alanine substitution of these two residues severely
inhibits IL-1 induced
NFkappaB and AP-1 activities, whereas TAK1 mutant with replacement of these two sites with acidic residues slightly enhances IL-1 induced NFkappaB and AP-1 activities compared with the TAK1 wild-type ... Consistently, TAK1 mutant with alanine substitution of these two residues severely inhibits IL-1 induced NFkappaB and AP-1 activities, whereas
TAK1 mutant with replacement of these two sites with acidic residues slightly
enhances IL-1 induced
NFkappaB and AP-1 activities compared with the TAK1 wild-type
Zhou et al., World J Gastroenterol 2008
(Adenocarcinoma...) :
Viable LBG or LBG- ( s ) pretreatment attenuated the expression of TLR4,
inhibited the phosphorylation of
TAK1 and p38MAPK, prevented the activation of
NF-kappaB , and consequently blocked IL-8 production
Fraczek et al., J Biol Chem 2008
:
The kinase activity of IL-1 receptor associated kinase 4 is required for interleukin-1 receptor/toll-like receptor induced
TAK1 dependent
NFkappaB activation
Minakawa et al., Biol Pharm Bull 2008
:
In this study, we examined the effect of ISGylation on tumor necrosis factor receptor associated factor ( TRAF) 6/transforming growth factor beta activated kinase (
TAK)-1 dependent
NF-kappaB activation
Wang et al., J Biol Chem 2009
(Carcinoma, Hepatocellular) :
Melittin, a major component of bee venom, sensitizes human hepatocellular carcinoma cells to tumor necrosis factor related apoptosis inducing ligand ( TRAIL ) -induced apoptosis by activating
CaMKII-TAK1-JNK/p38 and
inhibiting IkappaBalpha
kinase-NFkappaB ... In 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
Schuman et al., Blood 2009
:
The kinase
TAK1 is
essential for T-cell receptor ( TCR ) -mediated
nuclear factor kappaB (NF-kappaB) activation and T-cell development ... However, the
role of
TAK1 in B-cell receptor (BCR) mediated
NF-kappaB activation and B-cell development is not clear ... Thus,
TAK1 is
critical for B-cell maturation and BCR induced
NF-kappaB activation
Kumar et al., J Immunol 2009
(Inflammation) :
In this study, we tested the hypothesis that
TAK1 ( TGF-beta activated kinase 1 ) is
involved in TWEAK induced activation of
NF-kappaB and MAPK and expression of proinflammatory protein
Yamaguchi et al., Cell Biol Int 2009
(MAP Kinase Signaling System) :
JNK binding protein 1 regulates
NF-kappaB activation through TRAF2 and
TAK1 ... We also found that JNKBP1 could enhance the
NF-kappaB activation
induced by
TAK1 and TRAF2, and could promote TRAF2 polyubiquitination
Sun et al., Cell Signal 2009
:
Together, our results provide the genetic evidence that MEKK3 but not
TAK1 is
required for LPA receptor mediated
IKK-NF-kappaB activation
Henmi et al., Biochem J 2009
:
TAK1 ( transforming-growth-factor-beta activated kinase 1 ) mediates the IL-1 signalling pathway to NF-kappaB, and we observed that the
TAK1 induced
activation of
NF-kappaB was suppressed by PP2Ceta-2 expression
Lee et al., Biochim Biophys Acta 2009
:
DSCR1-1S also stimulated IL-1R mediated signaling pathways,
TAK1 activation,
NF-kappaB transactivation , and IL-8 production, all downstream consequences of IL-1R activation
Lamb et al., EMBO Rep 2009
(Inflammation) :
CagA physically associates with TAK1 and enhances its activity and
TAK1 induced
NF-kappaB activation through the tumour necrosis factor receptor associated factor 6-mediated, Lys 63-linked ubiquitination of TAK1
Yamazaki et al., Science signaling 2009
:
Here, we showed that
TAK1 mediated activation of
NF-kappaB required the transient formation of a signaling complex that included tumor necrosis factor receptor associated factor 6 ( TRAF6 ), MEKK3, and TAK1 ... After
TAK1 mediated activation of
NF-kappaB , TRAF6 subsequently activated NF-kappaB through MEKK3 independently of TAK1, thereby establishing continuous activation of NF-kappaB, which was required for the production of sufficient cytokines
Cheng et al., J Biomed Mater Res A 2010
(Inflammation...) :
The critical
role for
TAK1 in p38MAPK and
NFkappaB activation was as well confirmed by the inhibition of p38MAPK and NFkappaB activity following 5Z-7-oxozeaenol, a selective inhibitor of TAK1
Lluis et al., PloS one 2010
:
Overexpression of IKK2-EE, a constitutive activator of NF-kappaB, protected TAK1-/- MEFs against TRAIL killing, suggesting that
TAK1 activation of
NF-kappaB is critical for the viability of cells treated with TRAIL
Srivastava et al., J Biol Chem 2010
:
Although both the
TAK1 and the CARMA1 binding sites in ADAP are
essential for IkappaB alpha phosphorylation and degradation and
NF-kappaB nuclear translocation, only the TAK1 binding site in ADAP is necessary for IKK phosphorylation
Sakurai et al., Biochem Biophys Res Commun 1998
:
TGF-beta activated kinase 1 stimulates
NF-kappa B activation by an NF-kappa B-inducing kinase independent mechanism ... A dominant negative mutant of NIK did not inhibit
TAK1 induced
NF-kappa B activation ... These results suggest that
TAK1 induces
NF-kappa B activation through a novel NIK independent signaling pathway