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MAP3K3 — RELA
Text-mined interactions from Literome
Zhao et al., J Biol Chem 1999
:
We now show that MEKK2 and
MEKK3 can in vivo activate IKK-alpha and IKK-beta, induce site-specific IkappaBalpha phosphorylation, and, relatively modestly,
activate an
NF-kappaB reporter gene ... In addition, dominant negative versions of either IKK-alpha or IKK-beta abolish
NF-kappaB activation
induced by MEKK2 or
MEKK3 , thereby providing evidence that these IKKs mediate the NF-kappaB inducing activities of these MEKKs
Yang et al., Nat Immunol 2001
:
The essential
role of
MEKK3 in TNF induced
NF-kappaB activation ... Using mitogen activated protein kinase kinase kinase 3 ( MEKK3 ) -deficient fibroblast cells, we found that
MEKK3 plays a critical role in TNF induced
NF-kappaB activation
Che et al., Circ Res 2002
:
Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells :
role of Gab1 and
MEKK3 in TNF-alpha induced c-Jun and
NF-kappaB activation and adhesion molecule expression ... Gab1 associated with MEKK3, and a catalytically inactive form of
MEKK3 inhibited TNF-alpha induced c-Jun and
NF-kappaB transcriptional activation, suggesting a critical role for Gab1 and MEKK3 in TNF-alpha signaling
Chiao et al., Cancer 2002
(Carcinoma, Hepatocellular...) :
The current study data demonstrate that 1 ) RelA/NF-kappaB activity is activated constitutively in Hep3B cells, as determined by electrophoretic mobility shift assays ; 2 )
RelA/NF-kappaB reporter gene activity is
inhibited specifically by dominant negative mutants of IkappaB(alpha), IKK1, IKK2, MEKK1, and
MEKK3 and it is activated by overexpression of wild-type MEKK3, suggesting that upstream kinase cascades induce phosphorylation of IkappaB(alpha) and activate RelA/NF-kappaB in Hep3B cells ; 3 ) overexpression of the HBV x gene fails to activate NF-kappaB in HepG2 and Chang cell lines ; 4 ) The NF-kappaB-inducible gene, bcl-xl, is overexpressed in Hep3B cells and is inhibited by the proteosome inhibitor PS341, which prevents IkappaBalpha degradation and RelA/NF-kappaB activation ; and 5 ) inhibition of constitutive RelA/NF-kappaB activity by PS341 sensitizes Hep3B cells to doxorubicin induced apoptosis ... The current study data demonstrate that 1 ) RelA/NF-kappaB activity is activated constitutively in Hep3B cells, as determined by electrophoretic mobility shift assays ; 2 )
RelA/NF-kappaB reporter gene activity is
inhibited specifically by dominant negative mutants of IkappaB(alpha), IKK1, IKK2, MEKK1, and
MEKK3 and it is activated by overexpression of wild-type MEKK3, suggesting that upstream kinase cascades induce phosphorylation of IkappaB(alpha) and activate RelA/NF-kappaB in Hep3B cells ; 3 ) overexpression of the HBV x gene fails to activate NF-kappaB in HepG2 and Chang cell lines ; 4 ) The NF-kappaB-inducible gene, bcl-xl, is overexpressed in Hep3B cells and is inhibited by the proteosome inhibitor PS341, which prevents IkappaBalpha degradation and RelA/NF-kappaB activation ; and 5 ) inhibition of constitutive RelA/NF-kappaB activity by PS341 sensitizes Hep3B cells to doxorubicin induced apoptosis
Lerner-Marmarosh et al., Arterioscler Thromb Vasc Biol 2003
(Inflammation) :
Because
MEKK3 and Gab1 are
critical for TNF-alpha induced c-Jun and
NF-kappaB activation, we determined the role of SHP-2 phosphatase activity in MEKK3 signaling ... A catalytically inactive form of SHP-2 increased
MEKK3/Gab1 interaction and
inhibited MEKK3 ( but not MEKK1 ) -mediated c-Jun and
NF-kappaB activation
Samanta et al., J Biol Chem 2004
(Breast Neoplasms...) :
In this study, we established cell model systems to examine whether stable expression of
MEKK3 could
lead to increased
NFkappaB activity and confer resistance to apoptosis ... Thus, our results established that elevated expression of MEKK3 appears to be a frequent occurrence in breast and ovarian cancers and that overexpression of
MEKK3 in cells
leads to increased
NFkappaB activity and increased expression of cell survival factors and ultimately contributes to their resistance to apoptosis
Blonska et al., Mol Cell Biol 2004
:
We found that TNF-alpha induced
NF-kappaB activation was fully
restored by
MEKK3-DD in these cells
Fritz et al., J Biol Chem 2006
:
MEKK3 dependent
activation of an
NF-kappaB reporter gene as well as ERK, JNK, and p38 MAP kinases correlated with a requirement for serine at position 526
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
Qin et al., J Biol Chem 2006
:
TLR8 mediated
NF-kappaB and JNK activation are TAK1 independent and
MEKK3 dependent
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
Di et al., Cell Signal 2008
:
However, the mechanism by which
MEKK3 mediates
NF-kappaB signaling is not fully understood ... Expression of non phosphorylated TAK1 interferes with MEKK3 phosphorylation and
NF-kappaB reporter activity
induced by transient
MEKK3 expression or TNFalpha stimulation
Kim et al., J Endocrinol 2008
(Insulinoma) :
Overexpression of
MEKK3 , a possible mediator from the TNF-alpha receptor to the JNK/p38 and NK-kappaB signaling cascade,
increased the levels of phospho-JNK, phospho-p38, and
NF-kappaB , and reduced the glucose stimulated Ca(2) ( + ) influx and GSIS
Shinohara et al., Int Immunol 2009
:
The serine/threonine kinase
MEKK3 , also known as mitogen activated protein kinase kinase kinase 3, is a critical
activator of the transcription factor
NF-kappaB in innate immunity
Sun et al., Cell Signal 2009
:
MEKK3 is
required for lysophosphatidic acid induced
NF-kappaB activation ... Together, our results provide the genetic evidence that
MEKK3 but not TAK1 is
required for LPA receptor mediated
IKK-NF-kappaB activation
Samanta et al., Cancer 2009
(Cystadenocarcinoma, Serous...) :
The authors have demonstrated that
MEKK3 plays a critical role in cytokine mediated NFkappaB activation, and that stable expression of MEKK3 in cultured cells
leads to increased
NFkappaB activity
Sun et al., J Biol Chem 2010
:
Here we report the identification of two regulatory phosphorylation sites at Thr-516 and Ser-520 within the kinase activation loop that is essential for
MEKK3 mediated IkappaB kinase beta
(IKKbeta)/NF-kappaB activation
Sun et al., J Biol Chem 2010
:
Overexpression of PP2A catalytic subunit (PP2Ac) beta-isoform results in dephosphorylation of MEKK3 at Thr-516 and Ser-520 and termination of
MEKK3 mediated
NF-kappaB activation