2.7.11.10 ATP + a protein CHUK associates with the NF-kappaB inhibitory protein, IkappaB-alpha, in mammalian cells. CHUK specifically phosphorylates IkappaB-alpha on both Ser32 and Ser36, modifications that are required for targeted degradation of IkappaB-alpha via the ubiquitin-proteasome pathway 2.7.11.10 ATP + a protein the I kappa B/NF-kappa B system is a key determinant of mucosal inflammation and protection 2.7.11.10 ATP + a protein the expression of pkn1 is developmentally regulated to start immediately before spore formation. The enzyme plays an important role in the onset of proper differentiation 2.7.11.10 ATP + a protein phosphorylation of IkappaBs marks them out for destruction, thereby relieving their inhibitory effect on NF-kappaB 2.7.11.10 ATP + a protein phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses 2.7.11.10 ATP + Bcl phosphorylation at the C-terminus of Bcl by IKKbeta disrupts Bcl10/Malt1 association and Bcl10-mediated signaling 2.7.11.10 ATP + Bcl10 negative regulatory activity of the IKK complex in Bcl10 degradation, which is part of the regulatory mechanisms that precisely control the response to antigens, overview 2.7.11.10 ATP + IkappaB protein 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 2.7.11.10 ATP + IkappaBalpha - 2.7.11.10 ATP + IkappaBalpha a step in NF-kappaB activation, the IKK complex, composed of IKKalpha, IKKbeta, and NEMO/IKKgamma, is the convergence point for many diverse NFkappaB-activating stimuli including TNFalpha, LPS, and IL-1, overview, IKKbeta is the primary positive regulator of NFkappaB activity in inflammatory processes, is the molecular link between inflammation and cancer 2.7.11.10 ATP + IkappaBalpha degradation of IkappaBalpha 2.7.11.10 ATP + NF-kappaB - 2.7.11.10 ATP + protein p100 interaction with the NF-kappaB complex 2.7.11.10 ATP + protein p165 p65 is part of the IKKepsilon complex with p25, interaction with the NF-kappaB complex 2.7.11.10 ATP + [acetylated histone H3 protein] IKKalpha is required for histone function regulation in the nucleus 2.7.11.10 ATP + [GST-IkappaB protein] - 2.7.11.10 ATP + [GST-IkappaBalpha protein] - 2.7.11.10 ATP + [histone H3 protein] - 2.7.11.10 ATP + [histone H3 protein] histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression 2.7.11.10 ATP + [IFN regulatory factor 3 protein] IRF3 activation is triggered by IKKepsilon/TBK1-mediated phosphorylation on Ser396 2.7.11.10 ATP + [IkappaB protein] - 2.7.11.10 ATP + [IkappaB protein] 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 2.7.11.10 ATP + [IkappaB protein] inhibitor substrate is bound to NF-kappaB 2.7.11.10 ATP + [IkappaB protein] parasite IKKalpha, localized in parasitophorous vacuole membrane, activates mouse' intracellular NF-kappaB in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex 2.7.11.10 ATP + [IkappaB protein] phosphorylation of IkappaB results in its proteolytic degradation 2.7.11.10 ATP + [IkappaB protein] required for activation of NF-kappaB resulting in activation of signalling pathways 2.7.11.10 ATP + [IkappaB protein] signalling step of IKK bound to NFkappaB for subsequent ubiquitination of IkappaB and proteolytic degradation 2.7.11.10 ATP + [IkappaB protein] the IkappaBalpha subunit of NF-kappaB is phosphorylated at serine residues 32 and 36 2.7.11.10 ATP + [IkappaBalpha protein] - 2.7.11.10 ATP + [IkappaBalpha protein] enzyme is involved in activation of pro-inflammation signalling 2.7.11.10 ATP + [IkappaBalpha protein] parasite IKKalpha, localized in parasitophorous vacuole membrane, activates mouse' intracellular NF-kappaB through phosphorylation of host IkappaBalpha at Ser32 and Ser36 in early infection stage resulting in NF-kappaB nuclear translocation and subsequent gene expression independently from the host IKK complex 2.7.11.10 ATP + [IkappaBbeta protein] - 2.7.11.10 ATP + [IRF3 protein] phosphorylation at Ser396 by IKK-related IKKepsilon and TBK1 kinase 2.7.11.10 ATP + [leucine-rich repeat kinase 2 protein] catalyzed reaction of canonical IKKalpha and IKKbeta and IKK-related IKKepsilon and TBK1 kinase 2.7.11.10 ATP + [MYPT1] the enzyme phosphorylates MYPT1 at Thr853 2.7.11.10 ATP + [NFkappaB subunit p56] - 2.7.11.10 ATP + [optineurin protein] phosphorylation at Ser177 by IKK-related IKKepsilon and TBK1 kinase 2.7.11.10 ATP + [p73 protein] IKKalpha in the nucleus 2.7.11.10 ATP + [RelA/p65 protein] - 2.7.11.10 additional information activation of heterodimeric nuclear transcription factor NFkappaB is an essential step in inflammation, e.g. resulting in osteoarthritis, ulcerative colitis, asthma, and Crohn's disease, signalling step for phosphorylation, subsequent ubiquitination and proteolytic degradation of IkappaB, NFkappaB remains free after the reaction and is translocated to the nucleus, NFkappaB activation is also involved in development of diseases like cancer, gut ischemia-reperfusion, diabetes, or in transplant rejections, overview 2.7.11.10 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 2.7.11.10 additional information defective ubiquination of the NF-kappaB essential modifier/IkappaB kinase-gamma complex leads to impaired cellular NFkappaB signalling and hypohidrotic ectodermal dysplasia with immunodeficiency HED-ID 2.7.11.10 additional information enzyme is responsible for NFkappaB activation, specific inhibition of IkB kinase reduces hyperalgesia in inflammatory and neuropathic pain models in male Sprague-Dawley rats 2.7.11.10 additional information IkappaB kinases are essential key regulators of the NFkappaB pathways in the tooth development acting as stimulators, overview 2.7.11.10 additional information IKK activates and regulates NFkappaB important in intracellular signalling, overview 2.7.11.10 additional information IKK activates NF-kappaB through action of TNFalpha playing an important role in subsequent signaling pathways involved in e.g. apoptosis/cell survival, cell proliferation, and inflammation 2.7.11.10 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 2.7.11.10 additional information IKK activates TNFalpha-dependent signaling pathways inducing 5-fluoro-2'-deoxyuridine drug resistance in different cell lines, overview 2.7.11.10 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 2.7.11.10 additional information IKK is required for activation of NF-kappaB and subsequent signalling pathways 2.7.11.10 additional information IKK is responsible for activation of NFkappaB, herpesvirus HSV-1 potently induces IkappaB kinase IKK causing persistent induction of NFkappaB resulting in transactivation of HIV-1-LTR-regulated genes and induction of HIV-1 replication in infected T-cells 2.7.11.10 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 2.7.11.10 additional information IKK marks cytoplasmic NFkappaB inhibitors for proteolytic destruction playing a role in regulation of genetic cell cycle programs, IKK regulates nuclear translocation of transcription factor NFkappaB 2.7.11.10 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 2.7.11.10 additional information IKKbeta is required for activation of NFkappaB, IKKbeta induces expression of epithelial sodium channel alphabetagamma-ENaC in cell surfaces 2.7.11.10 additional information IKKbeta is required for regulation of NFkappaB activity and peripheral B cell survival and proliferation 2.7.11.10 additional information IKKbeta regulates the translocation of NF-kappaB from cytoplasm to nucleus earmarking the transcription factor for polyubiquitination and proteasome-mediated degradation, the cytokine TNFalpha-induced T-loop-phosphorylated IKKbeta becomes monoubiquitinated at Lyk163 proximal to the T-loop, mechanism of post-translational crosstalk, overview 2.7.11.10 additional information infection and genome insertion of human cytomegalovirus induces expression of the catalytic subunit IKK2 in the host cell which is required for viral induction of NF-kappaB activation and involved in viral replication and lytic cycle 2.7.11.10 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 2.7.11.10 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 2.7.11.10 additional information the IKK complex is responsible for NFkappaB regulation 2.7.11.10 additional information the noncanonical IkappaB kinase homologue IKKepsilon, beneath TANK-binding kinase-1 TBK-1, is required for activation of transcription factor NFkappaB and of interferon regulatory factor 3 IRF3, regulation and interaction, overview 2.7.11.10 additional information Vav-1 and IKKalpha subunit of IkappaB kinase functionally associate to induce NFkappaB activation in response to CD28 engagement 2.7.11.10 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 2.7.11.10 additional information hypoxia alters the cellular pool of IKKalpha and IKKbeta, and activates NFkappaB through a pathway involving activation of IkappaB kinase-beta, IKKbeta, leading to phosphorylation-dependent degradation of IkappaBalpha and liberation of NFkappaB, overview, hypoxia-induced activation of the NFkappaB pathway is independent of HIF-1alpha, prolyl hydroxylase-1 negatively regulates IKKbeta 2.7.11.10 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 2.7.11.10 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 2.7.11.10 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 2.7.11.10 additional information IKK is responsible for activation of NF-kappaB by initiating the degradation of the NF-kappaB inhibitor IkappaB, subunits IKKalpha and IKKgamma/NEMO, not IKKbeta, are required for reovirus-induced NF-kappaB activation and apoptosis, overview 2.7.11.10 additional information IKK-beta inhibition in vivo leads to reduction of rhinovirus-induced expression of CXCL8, CCL5, and IL-6, the enzyme is important in regulation of the NF-kappaB signaling pathway, overview 2.7.11.10 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 2.7.11.10 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 2.7.11.10 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 2.7.11.10 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 2.7.11.10 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 2.7.11.10 additional information IKKbeta subunit of IKK complex is essential for the activation of NF-kappaB in response to various proinflammatory signals, Cys179 of IkappaB kinase beta plays a critical role in enzyme activation by promoting phosphorylation of activation loop serines, overview 2.7.11.10 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 2.7.11.10 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 2.7.11.10 additional information mechanisms/pathways of activation and derepression of the IKK complex, regulation, detailed overview 2.7.11.10 additional information the IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories, IKKalpha is involved in the regulation of histone H3 phosphorylation and acetylation at specific gene promoters in hippocampus in the NF-kappaB pathway, inhibition of IKKalpha regulation results in impairments in fear memory reconsolidation, mechanism, overview