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Information on EC 2.7.11.10 - IkappaB kinase and Organism(s) Mus musculus and UniProt Accession Q9R0T8
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2.7.11.10 IkappaB kinaseIUBMB Comments
The enzyme phosphorylates IkappaB proteins at specific serine residues, which marks them for destruction via the ubiquitination pathway. Subsequent degradation of the IkB complex (IKK) activates NF-kappaB, a translation factor that plays an important role in inflammation, immunity, cell proliferation and apoptosis. If the serine residues are replaced by threonine residues, the activity of the enzyme is decreased considerably.
Specify your search results
Word Map
- 2.7.11.10
- nf-kappab
- necrosis
- factor-kappab
- tnf-alpha
- lps
- lipopolysaccharide
-
lps-induced
- il-1beta
- jnk
- monocyte
- endothelial
- parkinson
- factor-alpha
-
nf-kappab-dependent
- mapks
- proteasome
-
signal-regulated
- c-jun
- cox-2
-
transactivation
-
receptor-associated
-
antiapoptotic
- cyclooxygenase-2
- adaptor
-
dominant-negative
-
tnf-alpha-induced
-
toll-like
- chemokine
- nemo
-
leucine-rich
-
ikappab-alpha
- parthenolide
-
tnf-induced
- rig-i
- relb
- drug development
- analysis
-
factor-alpha-induced
- dithiocarbamate
- traf2
- molecular biology
- tak1
- medicine
- bcl-xl
-
il-1beta-induced
-
cytokine-induced
-
nf-kappab-mediated
-
k63-linked
- irf-3
-
polyubiquitination
- interleukin-1beta
-
tnf-alpha-mediated
-
lps-stimulated
- pharmacology
- icam-1
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
ikappabalpha, ikkbeta, ikappab kinase, ikkalpha, ikk complex, lrrk2 kinase, tank-binding kinase 1, ikk-beta, ikkepsilon, ikk-2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CHUK
IkappaB kinase alpha
IkappaB kinase beta
IKK
-
-
IKKalpha
IKKbeta
inhibitor of nuclear factor kappa B kinase beta subunit
-
inhibitor of nuclear factor kappa-B kinase alpha subunit
-
TANK-binding kinase 1
TBK1
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
ATP:[IkappaB protein] phosphotransferase
The enzyme phosphorylates IkappaB proteins at specific serine residues, which marks them for destruction via the ubiquitination pathway. Subsequent degradation of the IkB complex (IKK) activates NF-kappaB, a translation factor that plays an important role in inflammation, immunity, cell proliferation and apoptosis. If the serine residues are replaced by threonine residues, the activity of the enzyme is decreased considerably.
CAS REGISTRY NUMBER
COMMENTARY
159606-08-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + IkappaB protein
ADP + phosphorylated IkappaB
-
the enzyme targets the inhibitory IkappaB protein tightly bound to the transcription factor NF-kappaB for proteasomal degradation and allows the freed NF-kappaB to enter the nucleus where it can be transactivate its target gene, IKKalpha is involved in inflammation in macrophages
-
-
?
ATP + IkappaBalpha
ADP + phosphorylated IkappaBalpha
-
phosphorylation of IkappaBalpha at Ser32 and Ser36
-
-
?
ATP + IkappaBbeta
ADP + phosphorylated IkappaBbeta
-
phosphorylation of IkappaBalpha at Ser19 and Ser23
-
-
?
ATP + [GST-IkappaBalpha1-54 protein]
ADP + [GST-IkappaBalpha1-54 phosphoprotein]
-
-
-
-
?
ATP + [GST-IkappaBbeta protein]
ADP + [GST-IkappaBbeta phosphoprotein]
-
-
-
-
?
ATP + [IFN regulatory factor 3 protein (380-427)]
ADP + [IFN regulatory factor 3 phosphoprotein (380-427)]
-
the truncated mutant is a good substrate
-
-
?
ATP + [IkappaBbeta protein]
ADP + [IkappaBbeta phosphoprotein]
-
phosphorylation at Ser19 and Ser23
-
-
?
ATP + [IRF3 protein]
ADP + [IRF3 phosphoprotein]
-
phosphorylation at Ser396 by IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [leucine-rich repeat kinase 2 protein]
ADP + [leucine-rich repeat kinase 2 phosphoprotein]
ATP + [optineurin protein]
ADP + [optineurin phosphoprotein]
-
phosphorylation at Ser177 by IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [S386A IFN regulatory factor 3 protein]
ADP + [S386A IFN regulatory factor 3 phosphoprotein]
-
the mutant substrate is equally phosphorylated as the wild-type IRF3
-
-
?
ATP + [S396A IFN regulatory factor 3 protein]
ADP + [S396A IFN regulatory factor 3 phosphoprotein]
-
the mutant substrate is equally phosphorylated as the wild-type IRF3
-
-
?
ATP + [S402A/S404A/S405A IFN regulatory factor 3 protein]
ADP + [S402A/S404A/S405A IFN regulatory factor 3 phosphoprotein]
-
low activity with the IRF3 mutant
-
-
?
ATP + a protein
ADP + a phosphoprotein
the I kappa B/NF-kappa B system is a key determinant of mucosal inflammation and protection
-
-
?
ATP + a protein
ADP + a phosphoprotein
phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses
-
-
?
ATP + Bcl
ADP + phosphorylated Bcl
-
phosphorylation at the C-terminus of Bcl by IKKbeta disrupts Bcl10/Malt1 association and Bcl10-mediated signaling
-
-
?
ATP + Bcl
ADP + phosphorylated Bcl
-
phosphorylation at the C-terminus of Bcl by IKKbeta, inactive with a C-terminal 93 amino acid-deletion mutant of Bcl
-
-
?
ATP + protein p100
ADP + phosphorylated protein p100
-
interaction with the NF-kappaB complex
-
-
?
ATP + protein p100
ADP + phosphorylated protein p100
-
required for the interaction with the NF-kappaB complex
-
-
?
ATP + protein p165
ADP + phosphorylated protein p165
-
p65 is part of the IKKepsilon complex with p25, interaction with the NF-kappaB complex
-
-
?
ATP + protein p165
ADP + phosphorylated protein p165
-
required for the interaction with the NF-kappaB complex
-
-
?
ATP + [acetylated histone H3 protein]
ADP + [acetylated histone H3 phosphoprotein]
-
IKKalpha is required for histone function regulation in the nucleus
-
-
?
ATP + [acetylated histone H3 protein]
ADP + [acetylated histone H3 phosphoprotein]
-
phosphorylation at Ser10
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
-
histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
-
phosphorylation at Ser10 by IKK-alpha
-
-
?
ATP + [IFN regulatory factor 3 protein]
ADP + [IFN regulatory factor 3 phosphoprotein]
-
IRF3 activation is triggered by IKKepsilon/TBK1-mediated phosphorylation on Ser396
-
-
?
ATP + [IFN regulatory factor 3 protein]
ADP + [IFN regulatory factor 3 phosphoprotein]
-
phosphorylation on Ser396, and phosphorylation of Ser402/404/405 cluster in the C-terminal regulatory domain of IRF3 in vitro
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
-
661559, 662500, 662516, 662570, 662731, 662931, 662942, 663395, 663441, 703140, 704912, 705074, 705320, 705662, 722119, 722826
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
inhibition and degradation of IkappaB, an inhibitor of NF-kappaB retaining it in the cytoplasm, phosphorylation of IkappaB marks the protein for ubiquitination followed by degradation, activated NF-kappaB is translocated to the nucleus initiating signalling pathways, regulation mechanism, overview
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
inhibitor substrate is bound to NF-kappaB
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
phosphorylation of IkappaB results in its proteolytic degradation
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
required for activation of NF-kappaB resulting in activation of signalling pathways
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
-
IKKbeta-dependent phosphorylation and subsequent ubiquitin-dependent proteolytic degradation of IKKalpha, the 2 subunits have opposing function in NF-kappaB metabolism, overview
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
-
phosphorylation at Ser32 and Ser36
-
-
?
ATP + [IkappaBalpha protein]
ADP + [IkappaBalpha phosphoprotein]
-
phosphorylation on Ser32 and Ser36
-
-
?
ATP + [leucine-rich repeat kinase 2 protein]
ADP + [leucine-rich repeat kinase 2 phosphoprotein]
-
catalyzed reaction of canonical IKKalpha and IKKbeta and IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [leucine-rich repeat kinase 2 protein]
ADP + [leucine-rich repeat kinase 2 phosphoprotein]
-
phosphorylation of LRRK2 at Ser910 and Ser935 by IKKalpha and IKKbeta
-
-
?
ATP + [RelA/p65 protein]
ADP + [RelA/p65 phosphoprotein]
-
phosphorylation on Ser536 of the transactivation domain, dependent on lipopolysaccharide-induction, but not on Akt or p65
-
-
?
additional information
?
-
-
activation of NFkappaB by the catalytic subunit IKKbeta is required for signaling via the NFkappaB pathway in acute and systemic inflammation and for tissue protection
-
-
?
additional information
?
-
-
IkappaB kinases are essential key regulators of the NFkappaB pathways in the tooth development acting as stimulators, overview
-
-
?
additional information
?
-
-
IKK activates NF-kappaB which initiates signaling pathways that play critical roles in a variety of physiological and pathological processes, e.g. promotion of cell survival inducing production of apoptosis inhibitors in normal and cancer cells, pathways overview, IKK/NF-kappaB links inflammation to cancer, regulation of IKK, overview
-
-
?
additional information
?
-
-
IKK is involved in NF-kappaB activation, IkappaB kinase IKKbeta, but not IKKalpha, is a critical mediator of NF-kappaB-dependent osteoclast survival preventing TNFalpha-induced cell death, and is required for formation of fully functional bone-resorbing osteoclasts and for inflammation-induced bone loss
-
-
?
additional information
?
-
-
IKK is required for activation of NF-kappaB and subsequent signalling pathways
-
-
?
additional information
?
-
-
IKK is responsible for NF-kappaB activation by inactivating its inhibitor IkappaB, different inflammation stimuli induce distinct IKK activity profiles, molecular mechanism, overview
-
-
?
additional information
?
-
-
IKKalpha, not IKKbeta, is required for epidermal regeneration, IkappaB kinases are essential key regulators of the canonical and noncanonical NFkappaB pathways important for the expression of a wide variety of genes that are involved in the control of immune and inflammatory response, and in the regulation of cellular proliferation and survival, mechanism, overview
-
-
?
additional information
?
-
-
IKKbeta is required for activation of NFkappaB, IKKbeta induces expression of epithelial sodium channel alphabetagamma-ENaC in cell surfaces
-
-
?
additional information
?
-
-
IKKbeta is required for regulation of NFkappaB activity and peripheral B cell survival and proliferation
-
-
?
additional information
?
-
-
parasite Toxoplasma gondii IKKalpha, localized in parasitophorous vacuole membrane, activates the host intracellular NF-kappaB in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex
-
-
?
additional information
?
-
-
subunit IKKbeta controls the activation of NF-kappaB, important in inflammation, IKKalpha plays a role in lyphoid organogenesis and suppresses NF-kappaB activity by accelerating both the turnover of the NFkappaB subunits RelA and c-Rel, and their removal from pro-inflammatory gene promoters, inactivation of IKKalpha enhances inflammation and bacterial clearance in mice, overview
-
-
?
additional information
?
-
-
activated IKK2 is responsible for induction of leucocyte infiltration in pancreatic acini, the mutant ICC2CA in pancreatic acinar cells increases tissue damage of secretagogue induced experimental pancreatitits, the enzyme is involved in the proinflammatory IKK/NF-kappaB pathway, overview
-
-
?
additional information
?
-
-
IkappaB kinase beta plays a critical role in metallothionein-1 expression and protection against arsenic toxicity, two signaling pathways appear to be important for modulating arsenic toxicity. First, the IKK-NF-kappaB pathway is crucial for maintaining cellular metallothionein-1 levels to counteract reactive oxygen species accumulation, and second, when this pathway fails, excessive reactive oxygen species leads to activation of the MKK4-JNK pathway, resulting in apoptosis
-
-
?
additional information
?
-
-
IkappaB kinase beta plays an essential role in remodeling Carma1-Bcl10-Malt1 complexes upon T cell activation, T cell receptor signaling to IkappaB kinase/NF-kappaB is controlled by PKCtheta-dependent activation of the Carma1, Bcl10, and Malt1 CBM complex, IKKbeta triggers the CBM complex formation and phosphorylation of Bcl by PMA/ionomycin or CD3/CD28, regulation, overview
-
-
?
additional information
?
-
-
IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9, but IKK-a is dispensable for a cytoplasmic RNA helicase RIG-I-dependent cytosolic pathway-induced production of IFN-alpha in MEF cells, overview
-
-
?
additional information
?
-
-
IKK-related kinases tank-binding kinase 1 TBK1/IKKi and cullin-based ubiquitin ligases are involved in IFN regulatory factor-3, IRF-3, phosphorylation, activation, and degradation, IRF-3 activation is induced by viral infection, e.g. by HCMV, molecular mechanisms, detailed overview
-
-
?
additional information
?
-
-
IKKalpha and IKKbeta are distinctly involved in ERK1-dependent, but IkappaBalpha-P65- and p100-p52-independent, upregulation of MUC5AC mucin transcription in case of infection by Streptococcus pneumoniae, MUC5AC mucin induction also requires pneumolysin and TLR4-dependent MyD88-IRAK1-TRAF6 signaling, molecular mechanism, overview
-
-
?
additional information
?
-
-
IKKalpha enhances p73-mediated transactivation and pro-apoptotic functions in p53-deficient H1299 cells, stabilization of p73, but not of the antagonist p53, by nuclear IKKalpha mediates cisplatin-induced apoptosis, DNA damage-induced accumulation of both p53 and p73alpha is associated with the up-regulation of IKK-alpha and IKK-gamma, a functional interaction might exist between them in DNA damage-mediated apoptotic pathways
-
-
?
additional information
?
-
-
IKKalpha is involved in the noncanonical NF-kappaB activation pathway, and plays an essential role in thymic organogenesis required for the establishment of self-tolerance, overview
-
-
?
additional information
?
-
-
IKKalpha is not only a regulator of mammary epithelial proliferation, but is also an important contributor to ErbB2-induced oncogenesis, providing signals that maintain mammary tumor-initiating cells, IKKalpha activity is required for cyclin D1 induction and proliferation of lobuloalveolar epithelial cells, and is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells, overview
-
-
?
additional information
?
-
-
IKKepsilon is important in the regulation of the alternative NF-kappaB activation pathway involving p52 and p65, IKKepsilon interacts with p52 and promotes transactivation via p65
-
-
?
additional information
?
-
-
IKKepsilon, i.e. IKKi, is implicated in virus induction of interferon-beta, IFNbeta, and development of immunity, IKKepsilon functions in a redundant role to its ubiquitous counterpart, TBK1, in the activation of IRF3 and IRF7 ex vivo, IKKe determines ISGF3 binding specificity, regulaiton, overview
-
-
?
additional information
?
-
-
mechanisms/pathways of activation and derepression of the IKK complex, regulation, detailed overview
-
-
?
additional information
?
-
-
interaction analysis of IKKepsilon with NF-kappaB complex components/p25/p65 by immunoprecipitation and mass spectrometric analysis, overview
-
-
?
additional information
?
-
-
the enzyme activity is included in a complex formed of the scaffold protein NF-kappaB essential modulator, i.e. NEMO or IKKgamma, and the Ikkalpha and IKKbeta kinases, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + Bcl
ADP + phosphorylated Bcl
-
phosphorylation at the C-terminus of Bcl by IKKbeta disrupts Bcl10/Malt1 association and Bcl10-mediated signaling
-
-
?
ATP + IkappaB protein
ADP + phosphorylated IkappaB
-
the enzyme targets the inhibitory IkappaB protein tightly bound to the transcription factor NF-kappaB for proteasomal degradation and allows the freed NF-kappaB to enter the nucleus where it can be transactivate its target gene, IKKalpha is involved in inflammation in macrophages
-
-
?
ATP + protein p100
ADP + phosphorylated protein p100
-
interaction with the NF-kappaB complex
-
-
?
ATP + protein p165
ADP + phosphorylated protein p165
-
p65 is part of the IKKepsilon complex with p25, interaction with the NF-kappaB complex
-
-
?
ATP + [acetylated histone H3 protein]
ADP + [acetylated histone H3 phosphoprotein]
-
IKKalpha is required for histone function regulation in the nucleus
-
-
?
ATP + [histone H3 protein]
ADP + [histone H3 phosphoprotein]
-
histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression
-
-
?
ATP + [IFN regulatory factor 3 protein]
ADP + [IFN regulatory factor 3 phosphoprotein]
-
IRF3 activation is triggered by IKKepsilon/TBK1-mediated phosphorylation on Ser396
-
-
?
ATP + [IRF3 protein]
ADP + [IRF3 phosphoprotein]
-
phosphorylation at Ser396 by IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [leucine-rich repeat kinase 2 protein]
ADP + [leucine-rich repeat kinase 2 phosphoprotein]
-
catalyzed reaction of canonical IKKalpha and IKKbeta and IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + [optineurin protein]
ADP + [optineurin phosphoprotein]
-
phosphorylation at Ser177 by IKK-related IKKepsilon and TBK1 kinase
-
-
?
ATP + a protein
ADP + a phosphoprotein
the I kappa B/NF-kappa B system is a key determinant of mucosal inflammation and protection
-
-
?
ATP + a protein
ADP + a phosphoprotein
phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
-
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
inhibition and degradation of IkappaB, an inhibitor of NF-kappaB retaining it in the cytoplasm, phosphorylation of IkappaB marks the protein for ubiquitination followed by degradation, activated NF-kappaB is translocated to the nucleus initiating signalling pathways, regulation mechanism, overview
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
inhibitor substrate is bound to NF-kappaB
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
phosphorylation of IkappaB results in its proteolytic degradation
-
-
?
ATP + [IkappaB protein]
ADP + [IkappaB phosphoprotein]
-
required for activation of NF-kappaB resulting in activation of signalling pathways
-
-
?
additional information
?
-
-
activation of NFkappaB by the catalytic subunit IKKbeta is required for signaling via the NFkappaB pathway in acute and systemic inflammation and for tissue protection
-
-
?
additional information
?
-
-
IkappaB kinases are essential key regulators of the NFkappaB pathways in the tooth development acting as stimulators, overview
-
-
?
additional information
?
-
-
IKK activates NF-kappaB which initiates signaling pathways that play critical roles in a variety of physiological and pathological processes, e.g. promotion of cell survival inducing production of apoptosis inhibitors in normal and cancer cells, pathways overview, IKK/NF-kappaB links inflammation to cancer, regulation of IKK, overview
-
-
?
additional information
?
-
-
IKK is involved in NF-kappaB activation, IkappaB kinase IKKbeta, but not IKKalpha, is a critical mediator of NF-kappaB-dependent osteoclast survival preventing TNFalpha-induced cell death, and is required for formation of fully functional bone-resorbing osteoclasts and for inflammation-induced bone loss
-
-
?
additional information
?
-
-
IKK is required for activation of NF-kappaB and subsequent signalling pathways
-
-
?
additional information
?
-
-
IKK is responsible for NF-kappaB activation by inactivating its inhibitor IkappaB, different inflammation stimuli induce distinct IKK activity profiles, molecular mechanism, overview
-
-
?
additional information
?
-
-
IKKalpha, not IKKbeta, is required for epidermal regeneration, IkappaB kinases are essential key regulators of the canonical and noncanonical NFkappaB pathways important for the expression of a wide variety of genes that are involved in the control of immune and inflammatory response, and in the regulation of cellular proliferation and survival, mechanism, overview
-
-
?
additional information
?
-
-
IKKbeta is required for activation of NFkappaB, IKKbeta induces expression of epithelial sodium channel alphabetagamma-ENaC in cell surfaces
-
-
?
additional information
?
-
-
IKKbeta is required for regulation of NFkappaB activity and peripheral B cell survival and proliferation
-
-
?
additional information
?
-
-
parasite Toxoplasma gondii IKKalpha, localized in parasitophorous vacuole membrane, activates the host intracellular NF-kappaB in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex
-
-
?
additional information
?
-
-
subunit IKKbeta controls the activation of NF-kappaB, important in inflammation, IKKalpha plays a role in lyphoid organogenesis and suppresses NF-kappaB activity by accelerating both the turnover of the NFkappaB subunits RelA and c-Rel, and their removal from pro-inflammatory gene promoters, inactivation of IKKalpha enhances inflammation and bacterial clearance in mice, overview
-
-
?
additional information
?
-
-
activated IKK2 is responsible for induction of leucocyte infiltration in pancreatic acini, the mutant ICC2CA in pancreatic acinar cells increases tissue damage of secretagogue induced experimental pancreatitits, the enzyme is involved in the proinflammatory IKK/NF-kappaB pathway, overview
-
-
?
additional information
?
-
-
IkappaB kinase beta plays a critical role in metallothionein-1 expression and protection against arsenic toxicity, two signaling pathways appear to be important for modulating arsenic toxicity. First, the IKK-NF-kappaB pathway is crucial for maintaining cellular metallothionein-1 levels to counteract reactive oxygen species accumulation, and second, when this pathway fails, excessive reactive oxygen species leads to activation of the MKK4-JNK pathway, resulting in apoptosis
-
-
?
additional information
?
-
-
IkappaB kinase beta plays an essential role in remodeling Carma1-Bcl10-Malt1 complexes upon T cell activation, T cell receptor signaling to IkappaB kinase/NF-kappaB is controlled by PKCtheta-dependent activation of the Carma1, Bcl10, and Malt1 CBM complex, IKKbeta triggers the CBM complex formation and phosphorylation of Bcl by PMA/ionomycin or CD3/CD28, regulation, overview
-
-
?
additional information
?
-
-
IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9, but IKK-a is dispensable for a cytoplasmic RNA helicase RIG-I-dependent cytosolic pathway-induced production of IFN-alpha in MEF cells, overview
-
-
?
additional information
?
-
-
IKK-related kinases tank-binding kinase 1 TBK1/IKKi and cullin-based ubiquitin ligases are involved in IFN regulatory factor-3, IRF-3, phosphorylation, activation, and degradation, IRF-3 activation is induced by viral infection, e.g. by HCMV, molecular mechanisms, detailed overview
-
-
?
additional information
?
-
-
IKKalpha and IKKbeta are distinctly involved in ERK1-dependent, but IkappaBalpha-P65- and p100-p52-independent, upregulation of MUC5AC mucin transcription in case of infection by Streptococcus pneumoniae, MUC5AC mucin induction also requires pneumolysin and TLR4-dependent MyD88-IRAK1-TRAF6 signaling, molecular mechanism, overview
-
-
?
additional information
?
-
-
IKKalpha enhances p73-mediated transactivation and pro-apoptotic functions in p53-deficient H1299 cells, stabilization of p73, but not of the antagonist p53, by nuclear IKKalpha mediates cisplatin-induced apoptosis, DNA damage-induced accumulation of both p53 and p73alpha is associated with the up-regulation of IKK-alpha and IKK-gamma, a functional interaction might exist between them in DNA damage-mediated apoptotic pathways
-
-
?
additional information
?
-
-
IKKalpha is involved in the noncanonical NF-kappaB activation pathway, and plays an essential role in thymic organogenesis required for the establishment of self-tolerance, overview
-
-
?
additional information
?
-
-
IKKalpha is not only a regulator of mammary epithelial proliferation, but is also an important contributor to ErbB2-induced oncogenesis, providing signals that maintain mammary tumor-initiating cells, IKKalpha activity is required for cyclin D1 induction and proliferation of lobuloalveolar epithelial cells, and is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells, overview
-
-
?
additional information
?
-
-
IKKepsilon is important in the regulation of the alternative NF-kappaB activation pathway involving p52 and p65, IKKepsilon interacts with p52 and promotes transactivation via p65
-
-
?
additional information
?
-
-
IKKepsilon, i.e. IKKi, is implicated in virus induction of interferon-beta, IFNbeta, and development of immunity, IKKepsilon functions in a redundant role to its ubiquitous counterpart, TBK1, in the activation of IRF3 and IRF7 ex vivo, IKKe determines ISGF3 binding specificity, regulaiton, overview
-
-
?
additional information
?
-
-
mechanisms/pathways of activation and derepression of the IKK complex, regulation, detailed overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-methoxy-N-((6-(1-methyl-4-(methylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-7yl)pyridin-2-yl)methyl)acetamide
-
BMS-066, inhibitor of IKKbeta
4,8-dimethoxy-1-vinyl-beta-carboline
-
i.e. beta-carboline alkaloid C-1, isolated from Melia azedarach var. japonica, inhibits IKK activity by reduction of IKK phosphorylation and degradation, and activation and nuclear translocation of NF-kappaB and subsequent signalling pathways
4-(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline
-
BMS-345541, inhibitor of IKKbeta
arsenic trioxide
-
nonspecific for IKK, acts on a cystein ersidue in the activation loop
BMS345541
shows efficacy in a mouse model of collagen-induced arthritis without signs of major toxicology
additional information
-
two structurally unrelated kinase inhibitors, termed NG25 or 5Z-7-oxozeaenol, inhibit the TAK1 protein kinase, and therefore also inhibit activation of IKKalpha and IKKbeta
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cdc37
-
the chaperone protein associates with the IKK complex and is required for its TNFalpha-induced activation
-
HSP70
-
the chaperone protein associates with the IKK complex and is required for its TNFalpha-induced activation
-
Hsp90
-
the chaperone protein associates with the IKK complex and is required for its TNFalpha-induced activation
-
NEMO
-
i.e. NF-kappaB essential modifier, complexing with IkappaB kinase-gamma and ubiquitination, involving the zinc finger of NEMO and c-IAP1, are required for activation of the IkappaB kinase complex by inflammatory stimuli such as tumor necrosis factor TNFalpha
-
tumor necrosis factor TNFalpha
-
cytokines activate the IKK complex, mechanism, overview
-
TNFalpha
-
activates histone H3 phosphorylation activity, TNFalpha-induced activation of IKK-beta but not IKK-alpha leads to rapid NFkappaB activation and subsequent degradation of IkappaB
-
additional information
-
aldosterone regulates IKKbeta activity by enzyme induction
-
additional information
-
lipopolysaccharides from Escherichia coli induce enzyme activity versus RelA/p65 and NFkappaB activation in vivo, induction is not inhibited by LY294002, overview
-
additional information
-
lipopolysaccharides stimulate cytokine-mediated IKK activity being positively feedback regulated
-
additional information
-
TNF-alpha induced association of IKK-alpha with p65 and CBP
-
additional information
-
the IkappaB complex gets activated by phosphorylation, the enzyme activity is induced by proinflammatory cytokines and by oxidative and genotoxic stress, mechanisms/pathways of activation and derepression of the IKK complex, overview
-
additional information
-
virus-inducible expression of IKKepsilon, IKKepsilon is activated by IFNbeta
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
development of real-time imaging for continous enzyme detection and kinetics in intact cells and living mice utilizing a recombinant IkappaBalpha-firefly luciferase reporter construct
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
MCA3D (non-tumorigenic keratinocytes) highest IKK alpha expression, PDVC57 (moderately carcinogenic keratinocytes) show an important reduction in IKK alpha expression, HACa4 cells (highly tumorigenic) expression of IKK alpha is almost absent
-
IKKalpha and IKKbeta expression patterns in different developmental stages during gestation and in different tooth regions, overview
-
wild-type and IKKalpha- or IKKbeta-deficient embryonic fibroblast cell line infected with parasite Toxoplasma gondii, RH strain
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
IKKalpha shuttles between the nucleus and cytoplasm in a CRM1-dependent fashion
additional information
-
treatment with ATM inhibitors blocks the nuclear IKKalpha accumulation by cisplatin, suggesting that ATM plays a role in the nuclear translocation of IKKalpha
-
-
IKKbeta and IKKalpha are almost entirely cytoplasmic, IKK complex component scaffold protein NF-kappaB essential modulator, i.e. NEMO or IKKgamma, shuttles between the cytoplasm and the nucleus in a CRM-dependent manner
-
IKKalpha is located both in cytoplasm and nucleus, IKKbeta is predominantly cytoplasmic
-
IKK complex component scaffold protein NF-kappaB essential modulator, i.e. NEMO or IKKgamma, shuttles between the cytoplasm and the nucleus in a CRM-dependent manner
-
nuclear accumulation of IKKalpha occurs in response to CDDP, IKKalpha shuttles between the nucleus and cytoplasm in a CRM1-dependent fashion
-
IKKalpha is located both in cytoplasm and nucleus, e.g. TNF-alpha, a critical pro-inflammatory cytokine, and Helicobacter pylori stimulate IKKalpha nuclear translocation, mechanisms of IKKalpha nuclear translocation, overview. Kinase activation is required for IKKalpha to translocate into the nucleus
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
-
different patterns of beta-catenin activation in IKKalpha- and IKKbeta-deficient mouse embryonic fibroblast cells
malfunction
ablation of the kinase activity of enzyme IKKalpha affects plaque size and absolute smooth muscle cell number in atherosclerotic vessels differently depending on the vascular site examined
malfunction
enzyme silencing abolishes miR-199b-5p-stimulated inflammatory cytokines production and nuclear factor-kappaB activation
metabolism
-
LRRK2 does not play a major role in regulating the secretion of inflammatory cytokines induced by activation of the MyD88 pathway and LRRK2 kinase activity is not required for TLR-mediated Ser935 phosphorylation
metabolism
-
TAK1-mediated IKKalpha activation may regulate IRF3-dependent IFNbeta expression downstream of IKKepsilon/TBK1 activation in dendritic cells. IKKalpha-mediated phosphorylation of IRF3 promotes CBP recruitment and transcriptional activity
metabolism
-
when cells receive appropriate stimuli, such as TNF-alpha, a ternary IKK complex consisting of IKKalpha, IKKbeta and NEMO (IKKgamma) induces IkappaB phosphorylation, leading to IkappaB ubiquitination and proteasomal degradation that are required for liberation of NF-kappaB in the nucleus where it binds to specific promoter elements to activate gene expression. Regulations of cell cycle progression by nuclear IKKalpha, and nuclear function of IKKalpha in tumorigenesis and metastasis, overview
physiological function
-
IkappaB kinase beta is a key upstream regulator of the NF-kappaB pathway
physiological function
-
IkappaB kinase is a central kinase for nuclear factor-kappaB activation
physiological function
-
the IkappaB kinase complex is essential in transducing the signal-inducible activation of the transcription factor NF-kappaB in response to proinflammatory stimuli
physiological function
-
IKK catalyzes phosphorylation of LRRK2 at Ser910 and Ser935, the phosphorylation sites that regulate the binding of protein 14-3-3 to LRRK2. Phosphorylation of LRRK2 by IKKs plays in controlling macrophage biology. But increased phosphorylation of Ser910 and Ser935 induced by activation of the MyD88 pathway is insensitive to LRRK2 kinase inhibitors
physiological function
-
IKKalpha is required in dendritic cells for priming antigen-specific T cells, role for IKKalpha in regulation of IFN regulatory factor 3, IRF3, activity and the functional maturation of dendritic cells. Phosphorylation of the Ser402/404/405 cluster of residues is important for IRF3 activation and IFNbeta expression in response to viral infection. IKKalpha plays reciprocal roles in innate and adaptive immunity, limiting non-specific inflammation while promoting acquired antigen-specific immunity. IKKalpha activation in the haematopoietic compartment is critical for acquired immunity to the facultative intracellular pathogen Listeria monocytogenes. Requirement for IKKalpha in lymphotoxin beta signalling in radiation-resistant stromal cells
physiological function
-
the IkappaB kinase complex is the master kinase for NF-kappaB activation, in addition to mediating NF-kappaB signaling by phosphorylating IkappaB proteins during inflammatory and immune responses, the activation of the IKK complex also responds to various stimuli to regulate diverse functions independently of NF-kappaB. IKKalpha and IKKbeta have distinct physiological and pathological roles, while IKKbeta is predominantly cytoplasmic, IKKalpha shuttles between the cytoplasm and the nucleus with nuclear-specific roles of IKKalpha. Nuclear IKKalpha regulates NF-kappaB-dependent gene transcription and inflammation, regulatory functions of NF-kappaB, detailed overview. beta-Catenin-dependent transcription is decreased by IKKbeta but increased by IKKalpha. Regulation of apoptosis by nuclear IKKalpha. Nuclear IKKalpha is essential for cell cycle arrest and differentiation of keratinocyte in the epidermis and the morphogenesis of skeletal and craniofacial morphogenesis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). IKKE_MOUSE
717
0
80953
Swiss-Prot
other Location (Reliability: 3)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
the IkappaB kinase complex, IKK, contains two kinase subunits, IKKalpha and IKKbeta
heterotrimer
-
IkappaB kinase, IKK, consists of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit IKKgamma, NEMO
oligomer
-
the multisubunit IkappaB kinase complex is composed of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit termed NEMO or IKKgamma
additional information
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic NEMO/IKKgamma
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic NEMO/IKKgamma, complexes of IKKalpha and IKKgamma or IKKalpha homodimers are not stable
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic, regulatory NEMO/IKKgamma
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and noncatalytic, regulatory NEMO/IKKgamma
additional information
-
the IKK complex consists of 3 subunits: catalytic IKKalpha and IKKbeta, and regulatory IKKgamma
additional information
-
the enzyme activity is included in a complex formed of the scaffold protein NF-kappaB essential modulator, i.e. NEMO or IKKgamma, and the Ikkalpha and IKKbeta kinases, overview, the complex contains a zinc finger-like domain, N- and C-terminal coiled-coil domains, two alpha-helices and a leucine zipper
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
the IkappaB complex gets activated by phosphorylation and then autophosphorylates IkappaBalpha at Ser32 and Ser36
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K44A
S177E/S181E
-
site-directed mutagenesis, gain-of-function mutant of IKK2, IKK2-EE or IKK2CA, the mutant ICC2CA in pancreatic acinar cells increases tissue damage of secretagogue induced experimental pancreatitits, overview
additional information
K44A
-
site-directed mutagenesis, inactive ATP-binding site mutant, the kinase-deficient mutant IKK-alpha fails to stabilize p73
additional information
-
construction of IKK knockout mice as a model system for drug development
additional information
-
construction of IKKalpha-deficient and of IKKbeta-deficient mice and BM cell mutants, the mutants show defective osteoclastogenesis, wild-type osteoblasts can rescue osteoclastogenesis in IKKalpha- and IKKbeta-defective mutant BM cells, exogenic TNFalpha can rescue only IKKalpha-deficient mutants, TNFR1 can rescue IKKbeta-deficient osteoclast progenitors, but not prevent TNFalpha-induced apoptosis, overview
additional information
-
disruption of the gene encoding IKKbeta leads to apoptotic tissue damage, e.g. in mucosa, and prevention of systemic inflammatory response, which results in the multiple organ dysfunction syndrome MODS
additional information
-
IKKbeta-deficient B-cells are impaired in mitogenic responses to lipopolysaccharides, anti-CD40, and anti-IgM, and show high reduction of all peripheral B-cell subsets due to associated defects in cell survival
additional information
-
disruption of Ikbke-/-, the gene encoding IKKepsilon, results in a complete loss of the kinase in both mice and embryonic fibroblasts, generation of mice lacking IKKepsilon, the mice produce normal amounts of IFNbeta, but are hypersusceptible to viral infection because of a defect in the IFN signaling pathway, phenotype, overview
additional information
-
fibroblasts of ikkbeta-/- mice exhibit enhanced apoptosis in response to TNFalpha, NEMO/IKKgamma-deficient mice shows a phenotype with liver damage, but can be rescued by inactivation of the gene encoding the tumor necrosis factor-1, phenotypes, overview
additional information
-
generation of IKKalpha-/- mice, an autoimmune disease phenotype is induced in athymic nude mice by grafting embryonic thymus from IKKalpha-deficient mice
additional information
-
IKK knockout mice show downregulation of the CBM complex components Carma1 and Malt1, and impaired degradation of IkappaBalpha, overview
additional information
-
IkkalphaAA/AA 'knockin' mice, in which activation of IKKalpha is prevented by replacement of activation loop serines with alanines, exhibit delayed mammary gland growth during pregnancy, because IKKalpha activity is required for cyclin D1 induction and proliferation of lobuloalveolar epithelial cells, overview, retarded tumor development in response to either 7,12-dimethylbenzaanthracene or the ErbB2/Her2 transgene but had no effect on MMTV-v-Haras-induced cancer, overview
additional information
-
IKKbeta-/- 3T3 fibroblasts show decreased expression of antioxidant genes, such as metallothionein 1, Mt1, IKKbeta null cells display a marked increase in arsenic-induced reactive oxygen species accumulation, which leads to activation of the MKK4-c-Jun NH2-terminal kinase pathway, c-Jun phosphorylation, and apoptosis, overview
additional information
-
small interfering RNA-mediated knockdown of endogenous IKK-alpha inhibits the CDDP-mediated accumulation of p73alpha, the kinase-deficient mutant form of IKK-alpha interacts with p73alpha, but fails to stabilize it, CDDP-mediated accumulation of endogenous p73alpha is not detected in mouse embryonic fibroblasts prepared from IKK-alpha-deficient mice, and CDDP sensitivity is significantly decreased compared to wild-type MEFs, overview
additional information
-
TLR7/9-induced IFN-alpha production is severely impaired in constructed IKK-alpha-deficient plasmacytoid dendritic cells, whereas inflammatory cytokine induction is decreased but still occurrs, kinase-deficient IKK-alpha inhibits the ability of MyD88 to activate the Ifna promoter in synergy with IRF-7, expression of kinase-deficient IKK-alpha does not affect IRF-7-mediated promoter activation, but inhibits the enhancing effects ofMyD88
additional information
-
transfection of siRNA duplexes directed against IKKi and TBK1 downregulates the expression levels of both kinase isoforms by about 70%
additional information
conditional IKKbeta knockout mice are used in which the IKKbeta gene is specifically deleted in cells of myeloid lineage, including microglia, in the CNS. This deletion reduced IkappaB kinase (IKK) activity in cultured primary microglia by up to 40% compared with wild-type. Kainic acid-induced hippocampal neuronal cell death is reduced by 30% in knockout mice compared with wild-type mice
additional information
-
conditional IKKbeta knockout mice are used in which the IKKbeta gene is specifically deleted in cells of myeloid lineage, including microglia, in the CNS. This deletion reduced IkappaB kinase (IKK) activity in cultured primary microglia by up to 40% compared with wild-type. Kainic acid-induced hippocampal neuronal cell death is reduced by 30% in knockout mice compared with wild-type mice
additional information
gene disruption via homologous recombination reveals that activation of NF-kappaB in response to pathogen associated molecular patterns (PAMPs) and pro-inflammatory cytokines is dependent on IKKgamma/NEMO and on IKKbeta
additional information
gene disruption via homologous recombination reveals that activation of NF-kappaB in response to pathogen associated molecular patterns (PAMPs) and pro-inflammatory cytokines is dependent on IKKgamma/NEMO and on IKKbeta
additional information
-
gene disruption via homologous recombination reveals that activation of NF-kappaB in response to pathogen associated molecular patterns (PAMPs) and pro-inflammatory cytokines is dependent on IKKgamma/NEMO and on IKKbeta
additional information
gene disruption via homologous recombination reveals that IKKalpha, but not IKKbeta, kinase activity is required for activation of an alternative NF-kappaB signaling pathway based on processing of NF-kappaB2/p100:RelB complexes to NF-kappaB2/p52:RelB dimers. In addition, IKKalpha, and not IKKbeta, is required for differentiation of stratified epithelia, such as the epidermis, but this function does not require its protein kinase activity
additional information
gene disruption via homologous recombination reveals that IKKalpha, but not IKKbeta, kinase activity is required for activation of an alternative NF-kappaB signaling pathway based on processing of NF-kappaB2/p100:RelB complexes to NF-kappaB2/p52:RelB dimers. In addition, IKKalpha, and not IKKbeta, is required for differentiation of stratified epithelia, such as the epidermis, but this function does not require its protein kinase activity
additional information
-
gene disruption via homologous recombination reveals that IKKalpha, but not IKKbeta, kinase activity is required for activation of an alternative NF-kappaB signaling pathway based on processing of NF-kappaB2/p100:RelB complexes to NF-kappaB2/p52:RelB dimers. In addition, IKKalpha, and not IKKbeta, is required for differentiation of stratified epithelia, such as the epidermis, but this function does not require its protein kinase activity
additional information
Ikkalpha knockin mice are generated in which the two serine phosphoacceptor sites responsible for kinase activation are replaced with alanines. These mice express normal amounts of an IKKalpha protein whose kinase activity cannot be turned on in response to upstream stimuli. TRAMP mice, a mouse model for prostate carcinoma, that are rendered homozygous for the Ikkalpha knockin mutation are found to exhibit decelerated tumor development but eventually all died of primary prostate carcinoma. Knockin mice are found to display much fewer secondary site metastases than wild-type/TRAMP mice, indicating that IKK alpha is an enhancer for prostate metastasis
additional information
Ikkalpha knockin mice are generated in which the two serine phosphoacceptor sites responsible for kinase activation are replaced with alanines. These mice express normal amounts of an IKKalpha protein whose kinase activity cannot be turned on in response to upstream stimuli. TRAMP mice, a mouse model for prostate carcinoma, that are rendered homozygous for the Ikkalpha knockin mutation are found to exhibit decelerated tumor development but eventually all died of primary prostate carcinoma. Knockin mice are found to display much fewer secondary site metastases than wild-type/TRAMP mice, indicating that IKK alpha is an enhancer for prostate metastasis
additional information
-
Ikkalpha knockin mice are generated in which the two serine phosphoacceptor sites responsible for kinase activation are replaced with alanines. These mice express normal amounts of an IKKalpha protein whose kinase activity cannot be turned on in response to upstream stimuli. TRAMP mice, a mouse model for prostate carcinoma, that are rendered homozygous for the Ikkalpha knockin mutation are found to exhibit decelerated tumor development but eventually all died of primary prostate carcinoma. Knockin mice are found to display much fewer secondary site metastases than wild-type/TRAMP mice, indicating that IKK alpha is an enhancer for prostate metastasis
additional information
increased expression of IKKalpha in mouse tumorigenic epidermal cells (PDVC57) leads to changes in the differentiation pattern of the resulting squamous cell carcinomas, originating a distinct histological variant that resembles the human acantholytic squamous cell carcinomas (ASCC) variant
additional information
-
increased expression of IKKalpha in mouse tumorigenic epidermal cells (PDVC57) leads to changes in the differentiation pattern of the resulting squamous cell carcinomas, originating a distinct histological variant that resembles the human acantholytic squamous cell carcinomas (ASCC) variant
additional information
-
knock-out mice are generated lacking IKK1, IKK2, NEMO(IKKgamma), or both IKK1 and IKK2 in liver parenchymal cells: IKK1 and IKK2 ablation, sensitizes the liver to in vivo LPS challenge, uncovering a redundant function of the two IkappaB kinases in mediating canonical NF-kappaB signaling in hepatocytes and protecting the liver from TNF-induced failure. Knock out mice with combined ablation of IKK1 and IKK2 or IKK1 and NEMO spontaneously develop severe jaundice and fatal cholangitis characterized by inflammatory destruction of small portal bile ducts
additional information
mice lacking the beta subunit of IKK in myeloid cells are more susceptible to endotoxin shock than control mice, which might be a serious challenge for long-term IKKbeta inhibition
additional information
mice lacking the IKKbeta gene in hepatocytes surprisingly show many more and faster growing chemically-induced hepatocellular carcinoma, indicating that in hepatocytes IKKbeta inhibits chemically-induced hepatocellular carcinoma
additional information
mice lacking the IKKbeta gene in hepatocytes surprisingly show many more and faster growing chemically-induced hepatocellular carcinoma, indicating that in hepatocytes IKKbeta inhibits chemically-induced hepatocellular carcinoma
additional information
-
mice lacking the IKKbeta gene in hepatocytes surprisingly show many more and faster growing chemically-induced hepatocellular carcinoma, indicating that in hepatocytes IKKbeta inhibits chemically-induced hepatocellular carcinoma
additional information
targeted gene disruption of IKKbeta in intestinal epithelial cells leads to a 80% decline of colitis-associated cancer (CAC) induced by azoxymethane or dextran sulfate sodium salt administration
additional information
targeted gene disruption of IKKbeta in intestinal epithelial cells leads to a 80% decline of colitis-associated cancer (CAC) induced by azoxymethane or dextran sulfate sodium salt administration
additional information
-
targeted gene disruption of IKKbeta in intestinal epithelial cells leads to a 80% decline of colitis-associated cancer (CAC) induced by azoxymethane or dextran sulfate sodium salt administration
additional information
targeted gene disruption of IKKbeta in mature macrophages and neutrophils leads to a 50% decrease of tumor multiplicity of colitis-associated cancer (CAC) induced by azoxymethane or dextran sulfate sodium salt administration
additional information
targeted gene disruption of IKKbeta in mature macrophages and neutrophils leads to a 50% decrease of tumor multiplicity of colitis-associated cancer (CAC) induced by azoxymethane or dextran sulfate sodium salt administration
additional information
-
targeted gene disruption of IKKbeta in mature macrophages and neutrophils leads to a 50% decrease of tumor multiplicity of colitis-associated cancer (CAC) induced by azoxymethane or dextran sulfate sodium salt administration
additional information
-
using IKKbeta MCF7 knockout cells it is shown that in MCF7 cells TNF does not activate Akt and requires IKKbeta to activate mTOR
additional information
using TBK1-deficient mice it is shown by bone-marrow transfer experiments that TBK1-mediated signalling in haematopoietic cells is critical for the induction of antigen-specific B and CD41 T cells, whereas in non-haematopoietic cells TBK1 is required for CD81 T-cell induction
additional information
using TBK1-deficient mice it is shown that TBK1 mediates the adjuvant effect of DNA vaccines and is essential for its immunogenicity in mice. Plasmid-DNA-activated, TBK1-dependent signalling and the resultant type-I interferon receptor-mediated signalling is required for induction of antigen-specific B and T cells, which occurred even in the absence of innate immune signalling through a well known CpG DNA sensorToll-like receptor 9 (TLR9) or Z-DNA binding protein 1
additional information
-
generation of knock-in mice that express a mutant form of IKKalpha that cannot be activated, i.e. IKKalphaAA
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
adenoviral-mediated transient IKKbeta expression in enzyme-deficient cells significantly reduces apoptosis of the cells in response to arsenic
-
expression of FLAG-tagged wild-type and mutant enzymes in HEK-293 and HeLa cells, expression of the C-terminal fragment, comprising amino acids 541-716, of IKKepsilon with NF-kappaB2/p100/p52 in yeast two-hybrid cells
-
expression of IKKalpha in COS-7 cells, co-expression with p73alpha and His-tagged ubiquitin, analysis of ubiquitinated compounds
-
expression of IKKbeta in the yeast two-hybrid system, interaction with epithelial sodium channel alphabetagamma-ENaC, coexpression of IKKbeta and alphabeta-FLAG-gamma-ENaC in Xenopus laevis oocytes increases amilorid-sensitive current
-
expression of Myc-tagged IKK-alpha or IKK-beta in embryonic fibroblasts MEF cell line
-
expression of the enzyme using the baculovirus transfection method in HEK-293 cells
-
IKKbeta DNA fragments encoding the region covering the RelB-transactivation domain containing a putative leucine zipper motif, aa301-540, or helix-loop-helix and NEMO-binding domain, aa541-757, are inserted into pBHA and used as baites to screen a cDNA library, to express GST-fusion proteins in Escherichia coli, the gene fragments aa1-300, aa301-540, and aa541-756 are inserted into pGEX4T-1 or pCDNA3HA, all IKKbeta constructs, full length, aa1-300, aa301-757, aa1-540, and aa301-540-deleted forms, and IKKalpha are inserted into pCMV2-FLAG plasmids
-
overexpression of a gain-of-function mutant of IKK2, IKK2-EE or IKK2CA, in transgenic mice pancreas using an inducible genetic tet system, the mice additionally overexpress CMV-rtTA protein, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
curcumin decreases enzyme IKKbeta expression in activated microglial cells
Zymosan induces LRRK2 phosphorylation at S395 by IKK, stimulation of the Toll-like receptor pathway by MyD88-dependent agonists in bone marrow-derived macrophages or RAW264.7 macrophages induces IKK
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
development of real-time imaging for continous enzyme detection and kinetics in intact cells and living mice utilizing a recombinant IkappaBalpha-firefly luciferase reporter construct, system can be used for determination of kinetics/pharmacodynamics of potential selective inhibitors, and for investigations of NF-kappaB signalling pathway activation
medicine
molecular biology
medicine
-
IKKlapha may represent a specific target for treatment of ErbB2-positive breast cancer
medicine
-
results reveal a novel function of the two IkappaB kinases in cooperatively regulating liver immune homeostasis and bile duct integrity and suggest that IKK signaling may be implicated in human biliary diseases
medicine
TBK1 is a key signalling molecule for DNA-vaccine-induced immunogenicity, by differentially controlling DNA-activated innate immune signalling through haematopoietic and non-haematopoietic cells
medicine
-
IKKbeta-targeted NF-kappaB blockade is an attractive therapeutic approach for the prevention of colitis-associated tumors
medicine
-
inhibition of IkappaB kinase beta induces growth suppression and death in cells expressing wild-type, Imatinib-resistant, or the T315I Imatinib/Dasatinib-resistant forms of BCR-ABL
medicine
-
inhibition of IkappaB kinase beta restrains oncogenic proliferation of pancreatic cancer cells
molecular biology
-
IKK-alpha is a potential target for manipulating TLR-induced IFN-alpha production
molecular biology
IKK/nuclear factor-kappaB dependent microglia activation contributes to KA-induced hippocampal neuronal cell death in vivo through induction of inflammatory mediators
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kawai, J.; Shinagawa, A.; Shibata, K.; Yoshino, M.; Itoh, M.; et al.
Functional annotation of a full-length mouse cDNA collection
Nature
409
685-690
2001
Mus musculus (Q60680)
Jobin, C.; Sartor, R.B.
The I kappa B/NF-kappa B system: a key determinant of mucosalinflammation and protection
Am. J. Physiol.
278
C451-462
2000
Homo sapiens (O14920), Homo sapiens (O15111), Mus musculus (O88351), Mus musculus (Q60680), Rattus norvegicus (Q9QY78)
Nemoto, S.; DiDonato, J.A.; Lin, A.
Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase
Mol. Cell. Biol.
18
7336-7343
1998
Homo sapiens (O14920), Homo sapiens (O15111), Mus musculus (O88351), Mus musculus (Q60680), Rattus norvegicus (Q9QY78)
Connelly, M.A.; Marcu, K.B.
CHUK, a new member of the helix-loop-helix and leucine zipper families of interacting proteins, contains a serine-threonine kinase catalytic domain
Cell. Mol. Biol. Res.
41
537-549
1995
Homo sapiens (O15111), Mus musculus (Q60680)
Delhase, M.; Hayakawa, M.; Chen, Y.; Karin, M.
Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation
Science
284
309-313
1999
Homo sapiens (O15111), Mus musculus (Q60680)
Hu, M.C.; Wang, Y.; Qiu, W.R.; Mikhail, A.; Meyer, C.F.; Tan, T.H.
Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway activates IkappaB kinases (IKK-alpha/beta) and IKK-beta is a developmentally regulated protein kinase
Oncogene
18
5514-5524
1999
Mus musculus (O88351), Mus musculus
Nakano, H.; Shindo, M.; Sakon, S.; Nishinaka, S.; Mihara, M.; Yagita, H.; Okumura, K.
Differential regulation of IkappaB kinase alpha and beta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1
Proc. Natl. Acad. Sci. USA
95
3537-3542
1998
Mus musculus (O88351), Mus musculus (Q60680)
Shimada, T.; Kawai, T.; Takeda, K.; Matsumoto, M.; Inoue, J.; Tatsumi, Y.; Kanamaru, A.; Akira, S.
IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IkappaB kinases
Int. Immunol.
11
1357-1362
1999
Homo sapiens (Q14164), Mus musculus (Q9R0T8), Mus musculus
McKenzie, F.R.; Connelly, M.A.; Balzarano, D.; Muller, J.R.; Geleziunas, R.; Marcu, K.B.
Functional isoforms of IkappaB kinase alpha (IKKalpha) lacking leucine zipper and helix-loop-helix domains reveal that IKKalpha and IKKbeta have different activation requirements
Mol. Cell. Biol.
20
2635-2649
2000
Mus musculus (Q60680), Mus musculus
Mock, B.A.; Connelly, M.A.; McBride, O.W.; Kozak, C.A.; Marcu, K.B.
CHUK, a conserved helix-loop-helix ubiquitous kinase, maps to human chromosome 10 and mouse chromosome 19
Genomics
27
348-351
1995
Mus musculus (Q60680)
Ohazama, A.; Hu, Y.; Schmidt-Ullrich, R.; Cao, Y.; Scheidereit, C.; Karin, M.; Sharpe, P.T.
A dual role for Ikkalpha in tooth development
Dev. Cell
6
219-227
2004
Mus musculus
Lebowitz, J.; Edinger, R.S.; An, B.; Perry, C.J.; Onate, S.; Kleyman, T.R.; Johnson, J.P.
IkappaB kinase-beta (IKKbeta) modulation of epithelial sodium channel activity
J. Biol. Chem.
279
41985-41990
2004
Mus musculus
Molestina, R.E.; Sinai, A.P.
Host and parasite-derived IKK activities direct distinct temporal phases of NF-kappaB activation and target gene expression following Toxoplasma gondii infection
J. Cell Sci.
118
5785-5796
2005
Mus musculus, Toxoplasma gondii
Luo, J.L.; Kamata, H.; Karin, M.
IKK/NF-kappaB signaling: balancing life and death - a new approach to cancer therapy
J. Clin. Invest.
115
2625-2632
2005
Homo sapiens, Mus musculus
Ruocco, M.G.; Maeda, S.; Park, J.M.; Lawrence, T.; Hsu, L.C.; Cao, Y.; Schett, G.; Wagner, E.F.; Karin, M.
IkappaB kinase IKKbeta, but not IKKalpha, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss
J. Exp. Med.
201
1677-1687
2005
Mus musculus
Li, Z.W.; Omori, S.A.; Labuda, T.; Karin, M.; Rickert, R.C.
IKKbeta is required for peripheral B cell survival and proliferation
J. Immunol.
170
4630-4637
2003
Mus musculus
Yang, F.; Tang, E.; Guan, K.; Wang, C.Y.
IKKbeta plays an essential role in the phosphorylation of RelA/p65 on serine 536 induced by lipopolysaccharide
J. Immunol.
170
5630-5635
2003
Mus musculus
Yoon, J.W.; Kang, J.K.; Lee, K.R.; Lee, H.W.; Han, J.W.; Seo, D.W.; Kim, Y.K.
beta-Carboline alkaloid suppresses NF-kappaB transcriptional activity through inhibition of IKK signaling pathway
J. Toxicol. Environ. Health
68
2005-2017
2005
Mus musculus
Chen, L.W.; Egan, L.; Li, Z.W.; Greten, F.R.; Kagnoff, M.F.; Karin, M.
The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion
Nat. Med.
9
575-581
2003
Mus musculus, Mus musculus C57/BL6J
Gross, S.; Piwnica-Worms, D.
Real-time imaging of ligand-induced IKK activation in intact cells and in living mice
Nat. Methods
2
607-614
2005
Mus musculus
Yamamoto, Y.; Verma, U.N.; Prajapati, S.; Kwak, Y.T.; Gaynor, R.B.
Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression
Nature
423
655-659
2003
Homo sapiens, Mus musculus
Lawrence, T.; Bebien, M.; Liu, G.Y.; Nizet, V.; Karin, M.
IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammation
Nature
434
1138-1143
2005
Mus musculus
Werner, S.L.; Barken, D.; Hoffmann, A.
Stimulus specificity of gene expression programs determined by temporal control of IKK activity
Science
309
1857-1861
2005
Mus musculus
Yamamoto, Y.; Gaynor, R.B.
IkB kinases: key regulators of the NF-kB pathway
Trends Biochem. Sci.
29
72-79
2004
Homo sapiens, Mus musculus
Gloire, G.; Dejardin, E.; Piette, J.
Extending the nuclear roles of IkappaB kinase subunits
Biochem. Pharmacol.
72
1081-1089
2006
Mus musculus
Aleksic, T.; Baumann, B.; Wagner, M.; Adler, G.; Wirth, T.; Weber, C.K.
Cellular immune reaction in the pancreas is induced by constitutively active IkappaB kinase-2
Gut
56
227-236
2007
Mus musculus
Wietek, C.; Cleaver, C.S.; Ludbrook, V.; Wilde, J.; White, J.; Bell, D.J.; Lee, M.; Dickson, M.; Ray, K.P.; ONeill, L.A.
IkappaB kinase epsilon interacts with p52 and promotes transactivation via p65
J. Biol. Chem.
281
34973-34981
2006
Mus musculus
Furuya, K.; Ozaki, T.; Hanamoto, T.; Hosoda, M.; Hayashi, S.; Barker, P.A.; Takano, K.; Matsumoto, M.; Nakagawara, A.
Stabilization of p73 by nuclear IkappaB kinase-alpha mediates cisplatin-induced apoptosis
J. Biol. Chem.
282
18365-18378
2007
Mus musculus
Peng, Z.; Peng, L.; Fan, Y.; Zandi, E.; Shertzer, H.G.; Xia, Y.
A critical role for IkappaB kinase beta in metallothionein-1 expression and protection against arsenic toxicity
J. Biol. Chem.
282
21487-21496
2007
Mus musculus
Kinoshita, D.; Hirota, F.; Kaisho, T.; Kasai, M.; Izumi, K.; Bando, Y.; Mouri, Y.; Matsushima, A.; Niki, S.; Han, H.; Oshikawa, K.; Kuroda, N.; Maegawa, M.; Irahara, M.; Takeda, K.; Akira, S.; Matsumoto, M.
Essential role of IkappaB kinase alpha in thymic organogenesis required for the establishment of self-tolerance
J. Immunol.
176
3995-4002
2006
Mus musculus
Bibeau-Poirier, A.; Gravel, S.P.; Clement, J.F.; Rolland, S.; Rodier, G.; Coulombe, P.; Hiscott, J.; Grandvaux, N.; Meloche, S.; Servant, M.J.
Involvement of the IkappaB kinase (IKK)-related kinases tank-binding kinase 1/IKKi and cullin-based ubiquitin ligases in IFN regulatory factor-3 degradation
J. Immunol.
177
5059-5067
2006
Mus musculus
Ha, U.; Lim, J.H.; Jono, H.; Koga, T.; Srivastava, A.; Malley, R.; Pages, G.; Pouyssegur, J.; Li, J.D.
A novel role for IkappaB kinase (IKK) alpha and IKKbeta in ERK-dependent up-regulation of MUC5AC mucin transcription by Streptococcus pneumoniae
J. Immunol.
178
1736-1747
2007
Homo sapiens, Mus musculus, Mus musculus BALB/c
Wegener, E.; Oeckinghaus, A.; Papadopoulou, N.; Lavitas, L.; Schmidt-Supprian, M.; Ferch, U.; Mak, T.W.; Ruland, J.; Heissmeyer, V.; Krappmann, D.
Essential role for IkappaB kinase beta in remodeling Carma1-Bcl10-Malt1 complexes upon T cell activation
Mol. Cell
23
13-23
2006
Homo sapiens, Mus musculus
Hoshino, K.; Sugiyama, T.; Matsumoto, M.; Tanaka, T.; Saito, M.; Hemmi, H.; Ohara, O.; Akira, S.; Kaisho, T.
IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9
Nature
440
949-953
2006
Mus musculus
Cao, Y.; Luo, J.L.; Karin, M.
IkappaB kinase alpha kinase activity is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells
Proc. Natl. Acad. Sci. USA
104
15852-15857
2007
Mus musculus
Tenoever, B.R.; Ng, S.L.; Chua, M.A.; McWhirter, S.M.; Garcia-Sastre, A.; Maniatis, T.
Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity
Science
315
1274-1278
2007
Mus musculus
Cho, I.H.; Hong, J.; Suh, E.C.; Kim, J.H.; Lee, H.; Lee, J.E.; Lee, S.; Kim, C.H.; Kim, D.W.; Jo, E.K.; Lee, K.E.; Karin, M.; Lee, S.J.
Role of microglial IKKbeta in kainic acid-induced hippocampal neuronal cell death
Brain
131
3019-3033
2008
Mus musculus (O88351), Mus musculus
Moreno-Maldonado, R.; Ramirez, A.; Navarro, M.; Fernandez-Acenero, M.J.; Villanueva, C.; Page, A.; Jorcano, J.L.; Bravo, A.; Llanos Casanova, M.
IKKalpha enhances human keratinocyte differentiation and determines the histological variant of epidermal squamous cell carcinomas
Cell Cycle
7
2021-2029
2008
Homo sapiens (O15111), Homo sapiens, Mus musculus (Q60680), Mus musculus
Karin, M.
The IkappaB kinase - a bridge between inflammation and cancer
Cell Res.
18
334-342
2008
Mus musculus (O88351), Mus musculus (Q60680), Mus musculus
Niederberger, E.; Geisslinger, G.
The IKK-NF-kB pathway: a source for novel molecular drug targets in pain therapy?
FASEB J.
22
3432-3442
2008
Mus musculus (O88351), Rattus norvegicus (Q9QY78)
Dan, H.C.; Baldwin, A.S.
Differential involvement of IkappaB kinases alpha and beta in cytokine- and insulin-induced mammalian target of rapamycin activation determined by Akt
J. Immunol.
180
7582-7589
2008
Mus musculus, Homo sapiens (O15111)
Ishii, K.J.; Kawagoe, T.; Koyama, S.; Matsui, K.; Kumar, H.; Kawai, T.; Uematsu, S.; Takeuchi, O.; Takeshita, F.; Coban, C.; Akira, S.
TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines
Nature
451
725-729
2008
Mus musculus (A1L361)
Luedde, T.; Heinrichsdorff, J.; de Lorenzi, R.; De Vos, R.; Roskams, T.; Pasparakis, M.
IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver
Proc. Natl. Acad. Sci. USA
105
9733-9738
2008
Mus musculus
Kim, Y.L.; Kim, J.E.; Shin, K.J.; Lee, S.; Ahn, C.; Chung, J.; Kim, D.H.; Seong, J.Y.; Hwang, J.I.
GbetaL regulates TNFalpha-induced NF-kappaB signaling by directly inhibiting the activation of IkappaB kinase
Cell. Signal.
20
2127-2133
2008
Mus musculus
Hayakawa, Y.; Maeda, S.; Nakagawa, H.; Hikiba, Y.; Shibata, W.; Sakamoto, K.; Yanai, A.; Hirata, Y.; Ogura, K.; Muto, S.; Itai, A.; Omata, M.
Effectiveness of IkappaB kinase inhibitors in murine colitis-associated tumorigenesis
J. Gastroenterol.
44
935-943
2009
Mus musculus
Ochiai, T.; Saito, Y.; Saitoh, T.; Dewan, M.Z.; Shioya, A.; Kobayashi, M.; Kawachi, H.; Muto, S.; Itai, A.; Uota, S.; Eishi, Y.; Yamamoto, N.; Tanaka, S.; Arii, S.; Yamaoka, S.
Inhibition of IkappaB kinase beta restrains oncogenic proliferation of pancreatic cancer cells
J. Med. Dent. Sci.
55
49-59
2008
Homo sapiens, Mus musculus
Gillooly, K.M.; Pattoli, M.A.; Taylor, T.L.; Chen, L.; Cheng, L.; Gregor, K.R.; Whitney, G.S.; Susulic, V.; Watterson, S.H.; Kempson, J.; Pitts, W.J.; Booth-Lute, H.; Yang, G.; Davies, P.; Kukral, D.W.; Strnad, J.; McIntyre, K.W.; Darienzo, C.J.; Salter-Cid, L.; Yang, Z.; Wang-Iverson, D.B.; Burke, J.R.
Periodic, partial inhibition of IkappaB kinase beta-mediated signaling yields therapeutic benefit in preclinical models of rheumatoid arthritis
J. Pharmacol. Exp. Ther.
331
349-360
2009
Canis lupus familiaris, Homo sapiens, Mus musculus, Rattus norvegicus
Duncan, E.A.; Goetz, C.A.; Stein, S.J.; Mayo, K.J.; Skaggs, B.J.; Ziegelbauer, K.; Sawyers, C.L.; Baldwin, A.S.
IkappaB kinase beta inhibition induces cell death in Imatinib-resistant and T315I Dasatinib-resistant BCR-ABL+ cells
Mol. Cancer Ther.
7
391-397
2008
Mus musculus
Mancino, A.; Habbeddine, M.; Johnson, E.; Luron, L.; Bebien, M.; Memet, S.; Fong, C.; Bajenoff, M.; Wu, X.; Karin, M.; Caamano, J.; Chi, H.; Seed, M.; Lawrence, T.
I kappa B kinase alpha (IKKalpha) activity is required for functional maturation of dendritic cells and acquired immunity to infection
EMBO J.
32
816-828
2013
Homo sapiens, Mus musculus
Huang, W.; Hung, M.
Beyond NF-kappaB activation: Nuclear functions of IkappaB kinase alpha
J. Biomed. Sci.
20
3
2013
Homo sapiens, Mus musculus
Dzamko, N.; Inesta-Vaquera, F.; Zhang, J.; Xie, C.; Cai, H.; Arthur, S.; Tan, L.; Choi, H.; Gray, N.; Cohen, P.; Pedrioli, P.; Clark, K.; Alessi, D.R.
The IkappaB kinase family phosphorylates the Parkinsons disease kinase LRRK2 at Ser935 and Ser910 during Toll-like receptor signaling
PLoS ONE
7
e39132
2012
Mus musculus
Tilstam, P.V.; Soppert, J.; Hemmers, C.; Harlacher, E.; Doering, Y.; van der Vorst, E.P.C.; Schulte, C.; Alampour-Rajabi, S.; Theelen, W.; Asare, Y.; de Winther, M.P.J.; Lawrence, T.; Bernhagen, J.; Schober, A.; Zernecke, A.; Jankowski, J.; Weber, C.; Noels, H.
Non-activatable mutant of inhibitor of kappa B kinase alpha (IKKalpha) exerts vascular site-specific effects on atherosclerosis in Apoe-deficient mice
Atherosclerosis
292
23-30
2020
Mus musculus (Q60680)
Gao, F.; Shen, J.; Zhao, L.; Hao, Q.; Yang, Y.
Curcumin alleviates lipopolysaccharide (LPS)-activated neuroinflammation via modulation of miR-199b-5p/IkappaB kinase beta (IKKbeta)/nuclear factor kappa B (NF-kappaB) pathway in microglia
Med. Sci. Monit.
25
9801-9810
2019
Mus musculus (O88351)
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