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CD40 — NFKB1
Pathways - manually collected, often from reviews:
Text-mined interactions from Literome
Hsing et al., J Immunol 1999
:
Surprisingly, up-regulation of Fas, CD23, and ICAM-1 was partially independent, and up-regulation of LFA-1 was completely independent, of
CD40 induced
NF-kappaB activation
Revy et al., J Immunol 1999
:
However, the components of the NF-kappaB complexes were different in monocytes and B cells, because p50 is part of the
NF-kappaB complex
induced by
CD40 triggering in both monocytes and B cells, whereas p65 was only induced in B cells
Leo et al., J Biol Chem 1999
:
Differential requirements for tumor necrosis factor receptor associated factor family proteins in
CD40 mediated induction of
NF-kappaB and Jun N-terminal kinase activation ... Taken together, these findings reveal redundancy in the involvement of TRAF family proteins in
CD40 mediated
NF-kappaB induction and suggest that the membrane-proximal region of CD40 may stimulate the JNK pathway through a TRAF independent mechanism
Nakano et al., Proc Natl Acad Sci U S A 1999
:
Activation of either
NF-kappaB or c-Jun NH ( 2 ) -terminal kinase/stress activated protein kinase by tumor necrosis factor, CD27, and
CD40 was not abrogated in traf5 ( -/- ) mice
Baccam et al., Eur J Immunol 1999
:
However, the carboxy-terminal 32 amino acids are not, although these residues are required for
CD40 mediated
NF-kappaB activation
Furman et al., J Immunol 2000
(Leukemia, Lymphocytic, Chronic, B-Cell) :
In nonmalignant B cells,
CD40 ligation
results in nuclear translocation and activation of
NF-kappaB proteins ... In each case examined,
CD40 ligation further
augmented NF-kappaB activity and prolonged CLL cell survival in vitro
Gamper et al., Mol Immunol 2000
:
Over-expression of p62 ( aa 336-522 ) induces NF-kappaB activation in resting cells and augments
CD40 induced
NF-kappaB activation, but has no effect on control STAT1 reporter activity, either at baseline or after IFN-gamma induction
Brady et al., Biochem J 2000
:
The
activation of
NF-kappaB by
CD40 is a key process in facilitating this transcription by promoting the activation of the Cepsilon promoter
Andjelic et al., J Immunol 2000
:
Furthermore, our data indicate that PI-3K is indispensable for
CD40 mediated
NF-kappaB/Rel activation
Tone et al., Proc Natl Acad Sci U S A 2001
:
The interaction between
CD40 and CD40 ligand ( CD154 )
activates NF-kappa B , Jun N-terminal kinase, and Janus kinase/signal transducers and activators of transcription pathways and promotes B cell growth, differentiation, and survival as well as IL-12 production in macrophages and dendritic cells
Jain et al., Nat Immunol 2001
(Ectodermal Dysplasia...) :
Overall, the phenotype observed in XHM-ED patients shows that the putative zinc-finger domain of NEMO has a regulatory function and demonstrates the definite requirement of
CD40 mediated
NF-kappaB activation for B cell immunoglobulin class switching
Mizuno et al., Cell Signal 2001
:
However, EXTL3 did not affect the
CD40 mediated
NF-kappaB activation
Luftig et al., J Biol Chem 2001
:
Effects of the NIK aly mutation on
NF-kappaB activation by the Epstein-Barr virus latent infection membrane protein, lymphotoxin beta receptor, and
CD40 ... LMP1, an LMP1 transmembrane domain chimera with the LTbetaR signaling domain, and
LMP1/CD40 activate
NF-kappaB in wt or aly murine embryo fibroblasts ... On the other hand,
CD40 mediates
NF-kappaB activation through a kinase that interacts with a different component of the IKK complex
Schwabe et al., J Immunol 2001
:
CD40 activates
NF-kappa B and c-Jun N-terminal kinase and enhances chemokine secretion on activated human hepatic stellate cells ... Stimulation of
CD40 with CD40 ligand (CD40L) transfected baby hamster kidney cells
induces NF-kappaB , as demonstrated by the activation of I-kappaB kinase (IKK), increased NF-kappaB DNA binding, and p65 nuclear translocation
Bone et al., Int Immunol 2001
:
Nuclear
NF-kappaB is
induced in B cells by engagement of either the BCR or
CD40 or by stimulation with lipopolysaccharide (LPS)
Durandy et al., Curr Opin Immunol 2001
(Hypergammaglobulinemia...) :
Besides the well-known role of interaction between CD40-ligand and CD40, these pathological conditions definitively demonstrate the requirement of
CD40 mediated
NF-kappaB activation and the essential role of a newly described molecule, activation induced cytidine deaminase ( AID ), in B cell terminal differentiation
Jana et al., J Biol Chem 2001
:
However,
CD40 ligation alone
induced the activation of only
NF-kappaB but not of C/EBPbeta, suggesting that the activation of NF-kappaB alone by CD40 ligation is not sufficient to induce the expression of iNOS and that the activation of C/EBPbeta is also necessary for the expression of iNOS ...
Stimulation of IFN-gamma mediated activation of
NF-kappaB but not of C/EBPbeta by
CD40 ligation suggests that CD40 ligation stimulates the expression of iNOS in IFN-gamma treated BV-2 microglial cells through the stimulation of NF-kappaB activation
Afford et al., FASEB J 2001
(Liver Cirrhosis, Biliary) :
CD40 activation
induced , Fas dependent apoptosis and
NF-kappaB/AP-1 signaling in human intrahepatic biliary epithelial cells
Brady et al., Biochem Biophys Res Commun 2001
(Hypersensitivity) :
This study suggests that p38 MAPK is crucially important in mediating
CD40 activation of
NF kappa B which acts to induce C epsilon germline transcripts, ultimately facilitating IgE switching
Tone et al., J Biol Chem 2002
:
The
role of Sp1 and
NF-kappa B in regulating
CD40 gene expression ... We also show here that
CD40 expression in lipopolysaccharide stimulated cells is
up-regulated by
NF-kappaB through two distinct sites
Jana et al., J Neurochem 2002
:
However, CD40 ligation alone in the presence or absence of CD40 overexpression induced the activation of only NF-kappaB and not that of C/EBPbeta, suggesting that the
activation of
NF-kappaB alone by
CD40 ligation is not sufficient to induce the expression of TNF-alpha and that the activation of C/EBPbeta is also necessary for strong induction of TNF-alpha ... Taken together, these studies suggest that activation of both NF-kappaB and C/EBPbeta is important for strong induction of TNF-alpha and that
CD40 ligation
regulates the expression of TNF-alpha by modulating the activation of only
NF-kappaB but not that of C/EBPbeta
Mann et al., J Biol Chem 2002
:
CD40 induces interleukin-6 gene transcription in dendritic cells :
regulation by TRAF2, AP-1,
NF-kappa B , AND CBF1
Eliopoulos et al., J Virol 2002
(Carcinoma...) :
Consistent with this observation, catalytically inactive Tpl-2 also blocked
CD40 mediated
NF-kappaB activation, which largely depends on TRAF2
Ruby et al., Mol Pharmacol 2002
:
2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses tumor necrosis factor-alpha and
anti-CD40 induced activation of
NF-kappaB/Rel in dendritic cells : p50 homodimer activation is not affected
Ahmed-Choudhury et al., Mol Biol Cell 2003
:
CD40 ligation induced a rise in NF-kappaB activity in hepatocytes, which peaked at 2 h and returned to baseline by 24 h ; however, IHEC
CD40 ligation
resulted in a sustained up-regulation of
NF-kappaB ( > 24 h )
O'Sullivan et al., Curr Opin Hematol 2003
:
NFkappaB is
involved both in the regulation of
CD40 expression and in cell signaling after CD40 ligation
Longo et al., Circulation 2003
:
Overexpression of
CD40 , in a transient transfection system,
activates the transcription factor
NF-kappaB and upregulates IkappaBalpha, E-selectin, and tissue factor ( TF ) reporter activity ... In human coronary artery ECs ( HCAECs ), adenovirus mediated overexpression of A20 blocks physiological,
CD40 induced activation of
NF-kappaB , upstream of IkappaBalpha degradation ( Western blot ) and subsequently upregulation of ICAM-1, VCAM-1, and E-selectin ( flow cytometry )
Trompouki et al., Nature 2003
:
Downregulation of CYLD by RNA mediated interference augments both basal and
CD40 mediated activation of
NF-kappaB
Hostager et al., J Biol Chem 2003
:
Finally, we show that TRAF2 and TRAF6 have overlapping functions in
CD40 mediated
NF-kappaB activation and CD80 up-regulation
Gelbmann et al., Gut 2003
(Colitis, Ulcerative...) :
Inducible
CD40 expression
mediates NFkappaB activation and cytokine secretion in human colonic fibroblasts
Fotin-Mleczek et al., J Biol Chem 2004
:
Tumor necrosis factor receptor associated factor ( TRAF) 1 regulates
CD40 induced TRAF2 mediated
NF-kappaB activation ... Moreover, down-regulation of TRAF1 with small interfering RNAs enhanced
CD40/CD40 ligand
induced NF-kappaB activation but showed no effect on TNF signaling
Luftig et al., Proc Natl Acad Sci U S A 2004
:
LTbetaR and
CD40 activation of
p100/NF-kappaB2 is now known to be NIK/IKKalpha dependent and IKKbeta/IKKgamma independent
Inoue et al., J Immunol 2004
(MAP Kinase Signaling System) :
CD40 ligation also
resulted in the activation of
NF-kappaB
Dedeoglu et al., Int Immunol 2004
:
Induction of activation induced cytidine deaminase gene expression by IL-4 and
CD40 ligation is
dependent on STAT6 and
NFkappaB ... IL-4 induced STAT6 binding to a site in the 5 ' upstream region of the AID gene, while
CD40 ligation
induced NFkappaB binding to two sites in that region
Vakkila et al., J Immunol Methods 2004
:
NF-kappaB responses to IL-1beta,
CD40L , and LPS were donor dependent ( n=7 ), correlated with the quality of iDC preparations ( p=0.002 ), and IL-12 p70 production ( p=0.010 )
Mukundan et al., J Immunol 2005
:
However, ligation of a CD40 mutant lacking a functional TRAF6 binding site did not initiate inflammatory cytokine production, and this mutant was found to be defective in
CD40 mediated activation of ERK1/2, as well as IkappaB kinase (IKK) and
NF-kappaB
Chan et al., Biochem Biophys Res Commun 2005
:
Tpl2/COT1 was shown to participate in CD40 signaling based on the ability of a catalytically inactive mutant to suppress
CD40 mediated IkappaB kinase activation and induction of
NFkappaB-responsive promoters, without affecting signaling by TNF
Hauer et al., Proc Natl Acad Sci U S A 2005
:
In an attempt to delineate the role of individual TRAFs, we compared
NF-kappaB activation by
CD40 ( wt ) and CD40 mutants with different TRAF recruitment patterns
Davies et al., Cell Signal 2005
(Carcinoma) :
Moreover, no cross-talk between the two pathways was observed, as the specific suppression of PI3 kinase with chemical inhibitors did not influence
CD40 mediated IkappaBalpha phosphorylation and degradation or
NF-kappaB binding and transactivation
Qin et al., Blood 2005
:
LPS
induces CD40 gene expression through the activation of
NF-kappaB and STAT-1alpha in macrophages and microglia ... In this study, we describe that LPS is a strong inducer of
CD40 expression in macrophages and microglia, which occurs at the transcriptional level and
involves the activation of the transcription factors
nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription 1alpha ( STAT-1alpha ) ... These results indicate that both LPS induced
NF-kappaB activation and endogenous production of IFN-beta that subsequently induces STAT-1alpha activation
play critical roles in the transcriptional activation of the
CD40 gene by LPS
Laxmanan et al., J Am Soc Nephrol 2005
:
By electrophoretic mobility shift assay, it was confirmed that
CD40 signaling
induced the transcriptional activation of HO-1 through the binding of
NF-kappaB to its promoter
Lin et al., Biol Pharm Bull 2005
:
Our results suggest that CRP increases activation of
NF-kappaB and
induces CD40 expression in HUVECs partly via activation of NF-kappaB
Davies et al., Mol Cell Biol 2005
:
In fibroblasts lacking TRAF2 or in carcinoma cells in which TRAF2 has been depleted by RNA interference, the
CD40 mediated activation of
NF-kappaB and JNK is significantly reduced, and the activation of p38 and Akt is severely impaired ... Interestingly, whereas the TRAF6 interacting membrane-proximal domain of CD40 has a minor role in signal transduction, studies utilizing TRAF6 knockout fibroblasts and RNA interference in epithelial cells reveal that the
CD40 induced
activation of
NF-kappaB , JNK, p38, and Akt requires the integrity of TRAF6
Poppema et al., Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program 2005
(Hodgkin Disease) :
A key role is played by the presence of constitutive nuclear factor
(NF)-kappaB , which is
induced by LMP1, as well as by CD30,
CD40 , tumor necrosis factor (TNF)-alpha, and Notch1 interactions, and results in the upregulation of at least 45 genes including chemokines, cytokines, receptors, apoptotic regulators, intracellular signaling molecules, and transcription factors
Horie et al., Leukemia 2006
(Leukemia, Lymphocytic, Chronic, B-Cell) :
Dehydroxymethylepoxyquinomicin also inhibited
NF-kappaB induced by
CD40 and enhanced fludarabine mediated apoptosis of CLL cells
Lee et al., Arthritis Rheum 2006
(Arthritis, Rheumatoid) :
CD40 ligation of RASFs also
induced activation of ERK-1/2, p38 MAPK, and
NF-kappaB and up-regulation of CD40 ligation induced RANKL expression, whereas osteoclastogenesis was reduced in RASFs transfected with a dominant negative mutant of IkappaB alpha or by an NF-kappaB inhibitor
Shiraki et al., Int J Mol Med 2006
(Hepatitis C, Chronic...) :
The
effect of
CD40 stimulation on
NF-kappaB activation was determined in NF-kappaB reporter gene transfected HepG2 cells with the Luciferase assay
Frasca et al., Exp Gerontol 2007
:
Therefore,
NF-kappaB is not involved in the decreased
response of old B cells to
anti-CD40/IL-4
Qin et al., J Immunol 2006
:
We previously demonstrated that LPS induction of
CD40 in macrophages/microglia
involves both
NF-kappaB activation and LPS induced production of IFN-beta, which subsequently activates STAT-1alpha
Lich et al., J Immunol 2007
(Inflammation) :
In this report, we show that Monarch-1 inhibits
CD40 mediated activation of
NF-kappaB via the non-canonical pathway in human monocytes
Browatzki et al., Eur J Med Res 2007
:
Experiments with PI-1, an inhibitor of the IkappaB-a degrading proteasome complex, demonstrated
involvement of the transcription factor
NF-kappaB in ET-1 induced
CD40 expression
Lee et al., J Leukoc Biol 2007
:
IFN-gamma induced
CD40 expression
involves activation of STAT-1alpha as well as
NF-kappaB activation through an autocrine response to IFN-gamma induced TNF-alpha production
Stuhlmeier et al., J Immunol 2007
(Necrosis) :
Apis mellifera venom and melittin block neither NF-kappa
B-p50-DNA interactions nor the
activation of
NF-kappa B , instead they activate the transcription of proinflammatory genes and the release of reactive oxygen intermediates
Lam et al., J Biol Chem 2007
:
Blocking the activity of Akt demonstrated a crucial role for Akt in translocation of STAT-1alpha and
NF-kappaB to the nucleus and
activation of the
CD40 promoter
Qiao et al., J Immunol 2007
:
Mechanistically, Cbl-b selectively down-modulates
CD40 induced activation of
NF-kappaB and JNK
Rowland et al., J Immunol 2007
:
Our previous experiments with TRAF2-deficient B cell lines suggest that TRAF6 and TRAF2 may have redundant roles in
CD40 mediated
NF-kappaB activation ... Consistent with this hypothesis, we found
CD40 mediated
activation of
NF-kappaB intact in TRAF6-deficient cells and defective in cells lacking both TRAF2 and TRAF6
Hostager et al., Immunol Res 2007
:
TRAF6 contributes to the
CD40 mediated activation of
NF-kappaB , stress activated protein kinases, and perhaps other signaling molecules
Wu et al., Toxicol Appl Pharmacol 2008
:
Involvement of mitogen activated protein kinases and
NFkappaB in LPS induced
CD40 expression on human monocytic cells ... Further studies using immunoblotting and pharmacological inhibitors revealed that mitogen activated protein kinases ( MAPKs ) and
NFkappaB were activated by LPS exposure and
involved in LPS induced
CD40 expression ... In summary, LPS induced
CD40 expression in monocytic cells
involves MAPKs and
NFkappaB
Vaitaitis et al., PloS one 2008
:
CD40 engagement of Th40 cells
induces Nf-kappaB DNA binding activity and anti-apoptotic Bcl-X ( L ) expression in all three mouse strains
Moschonas et al., Mol Cell Biol 2008
(Neoplasms) :
We show that unlike interferon signaling, which triggers the STAT1 mediated transcriptional activation of IRF-1, the ligation of
CD40 in carcinomas induces the rapid upregulation of IRF-1 in a STAT1 independent but
NF-kappaB dependent manner
Zhu et al., Transplant Proc 2008
:
We undertook this study to determine whether CD154-CD40 interactions induced human endothelial cell ( EC ) activation via the nuclear factor (NF)-kappaB pathway, and whether the upregulation of monocyte derived
CD40 and CD80 is
NF-kappaB pathway
dependent ... The
NF-kappaB inhibitor
suppressed upregulation of monocytederived
CD40 and CD80
Larangé et al., J Leukoc Biol 2009
:
We found that upon TLR7 and TLR8 activation, JNK and
NF-kappaB positively
regulated the expression of CCR7, CD86, CD83, and
CD40 and the production of IL-6 and IL-12p40
Wu et al., Inflamm Res 2009
:
Ang II upregulates the expression of TLR4 by RPMCs, resulting in enhanced
NF-kappaB signaling and
induction of
CD40 , TNF-alpha, and IL-6 expression
Hostager et al., PloS one 2010
:
We found that a mutant HOIP molecule engineered to lack ubiquitin ligase activity inhibited the
CD40 mediated activation of
NF-kappaB
Song et al., PloS one 2011
(Carotid Artery Injuries...) :
In vitro data revealed that
CD40 deficiency
blocked CD40L induced
NF-kB p65 nuclear translocation in leukocytes
Vakkila et al., Drug Discov Today 2005
:
NF-kappaB responses to IL-1beta,
CD40L , and LPS were donor dependent ( n = 7 ), correlated with the quality of iDC preparations ( p = 0.002 ), and IL-12 p70 production ( p = 0.010 )
Jin et al., PloS one 2013
:
Moreover, sCD40L strongly stimulates neutrophil oxidative burst via
CD40 dependent activation of
PI3K/NF-KB , but independent of Mac-1 and PKC?
Francis et al., Int Immunol 1995
:
Despite the marked similarity in transcription factor induction triggered through CD40 and slg, differences in the intracellular signaling pathways utilized were apparent in that protein kinase C ( PKC ) depletion did not affect
CD40 mediated induction of
NF-kappa B even as induction by anti-Ig was abolished
Rothe et al., Science 1995
:
A truncated derivative of TRAF2 lacking an amino-terminal RING finger domain was a dominant negative inhibitor of
NF-kappa B activation
mediated by TNF-R2 and
CD40
Ledbetter et al., Circ Shock 1994
:
Activation of
NF-kappa B occurred in RAJI cells by G28-5 or by gp39 treatment, and was
CD40 crosslinking
dependent ... These results suggest that activation of
NF-kappa B is
involved in some
CD40 receptor signals and may be related to CD40 effects on stimulation or inhibition of apotosis
Rothe et al., Proc Natl Acad Sci U S A 1996
:
TRAF2 is required for
CD40- and TNF mediated
activation of the transcription factor
NF-kappa B
Lin et al., Mol Cell Biol 1996
:
Activation of
NF-kappaB/Rel by
CD40 engagement induces the mouse germ line immunoglobulin Cgamma1 promoter
Ware et al., J Cell Biochem 1996
:
The TRAF family of Zn RING/finger proteins bind to TNFR80 ;
CD40 and LT beta R are
involved in induction
NF kappa B and cell survival
Yanagihara et al., Cell Immunol 1997
(Burkitt Lymphoma) :
These results indicate that IL-4 and ligation of
CD40 induce
NF-kappa B expression via at least a mechanism dependent on the PI3-kinase pathway and suggest that NF-kappa B sensitive to NAC may play a role in regulating germline C epsilon transcription
Hsing et al., J Immunol 1997
(Lymphoma, B-Cell) :
This suggests that in B cells,
CD40 induced
NF-kappa B activation can occur independently of TRAF2 and TRAF5 association ... Proteasome dependent inhibitory kappa B alpha ( I kappa B alpha ) and I kappa B beta degradation occurred downstream of CD40 ligation and preceded
CD40 mediated
NF-kappa B nuclear translocation
Kashiwada et al., J Exp Med 1998
:
CD40 activates
nuclear factor kappa B (NF kappa B) and the mitogen activated protein kinase ( MAPK ) subfamily, including extracellular signal regulated kinase ( ERK )
Yanagihara et al., J Allergy Clin Immunol 1997
:
These results suggest that coordination of NF-kappaB and STAT6 may be required for induction of germline Cepsilon transcription by IL-4, and that
CD40 mediated
NF-kappaB activation may be important in regulating both enhancement of germline Cepsilon transcription and class switching to IgE
Jeppson et al., J Immunol 1998
:
These data indicate that both IL-4 and
anti-CD40 are
required to induce
NF-kappa B activation and IL-6 transcription and production, and implicate these events in a signaling pathway augmenting IgE production in human B lymphocytes
Lazaar et al., J Immunol 1998
:
In addition, inhibition of calcium influx inhibited both
CD40 mediated
NF-kappaB activation and enhancement of IL-6 secretion
Craxton et al., J Immunol 1998
(Lymphoma, B-Cell) :
SB203580 also significantly reduced expression of a reporter gene driven by a minimal promoter containing four NF-kappaB elements, indicating a requirement for the p38 MAPK pathway in
CD40 induced
NF-kappaB activation ... However,
CD40 mediated
NF-kappaB binding was not affected by SB203580, suggesting that NF-kappaB may not be a direct target for the CD40 induced p38 MAPK pathway
Hornung et al., Eur J Immunol 1998
(Lymphoma, B-Cell) :
At the molecular level,
CD40 has been shown to
activate nuclear factor kappaB (NF-kappaB) and stress activated protein kinase ( SAPK )
Lee et al., Eur J Immunol 1998
:
Furthermore, transfection of WEHI 231 cells with a plasmid encoding Mn-superoxide dismutase interferes with
CD40 induced
NF-kappaB activation, providing further support for ROI involvement in this pathway
Tsukamoto et al., Proc Natl Acad Sci U S A 1999
:
Although four members of the tumor necrosis factor receptor associated factor ( TRAF ) family, including TRAF2, TRAF3, TRAF5, and TRAF6, bind to the CD40 cyt, how each TRAF protein contributes to the
NFkappaB activation by
CD40 is not clear
Lee et al., Proc Natl Acad Sci U S A 1999
(Lymphoma, B-Cell) :
Specificities of CD40 signaling : involvement of TRAF2 in
CD40 induced
NF-kappaB activation and intercellular adhesion molecule-1 up-regulation ... Overexpression of a dominantly active IkappaBalpha strongly inhibited
CD40 induced
NF-kappaB activation, ICAM-1 promoter activity, and cell-surface ICAM-1 up-regulation