The kinase TAK1 can activate the NIK-IκB as well as the MAP kinase cascade in the IL-1 signalling pathway
Copyright policy )The kinase TAK1 can activate the NIK-IκB as well as the MAP kinase cascade in the IL-1 signalling pathway
Interleukin-1 (IL-1) is a proinflammatory cytokine that has several effects in the inflammation process. When it binds to its cell-surface receptor, IL-1 initiates a signalling cascade that leads to activation of the transcription factor NF-kappaB and is relayed through the protein TRAF6 and a succession of kinase enzymes, including NF-kappaB-inducing kinase (NIK) and I kappaB kinases (IKKs). However, the molecular mechanism by which NIK is activated is not understood. Here we show that the MAPKK kinase TAK1 acts upstream of NIK in the IL-1-activated signalling pathway and that TAK1 associates with TRAF6 during IL-1 signalling. Stimulation of TAK1 causes activation of NF-kappaB, which is blocked by dominant-negative mutants of NIK, and an inactive TAK1 mutant prevents activation of NF-kappaB that is mediated by IL-1 but not by NIK. Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway.
TNF Receptor-Associated Factor 6, Threonine, Recombinant Fusion Proteins, JNK Mitogen-Activated Protein Kinases, NF-kappa B, Proteins, Protein Serine-Threonine Kinases, MAP Kinase Kinase Kinases, Precipitin Tests, Cell Line, I-kappa B Kinase, Enzyme Activation, Multienzyme Complexes, Mutagenesis, Calcium-Calmodulin-Dependent Protein Kinases, Serine, Mitogen-Activated Protein Kinases, Phosphorylation, Interleukin-1, Signal Transduction
TNF Receptor-Associated Factor 6, Threonine, Recombinant Fusion Proteins, JNK Mitogen-Activated Protein Kinases, NF-kappa B, Proteins, Protein Serine-Threonine Kinases, MAP Kinase Kinase Kinases, Precipitin Tests, Cell Line, I-kappa B Kinase, Enzyme Activation, Multienzyme Complexes, Mutagenesis, Calcium-Calmodulin-Dependent Protein Kinases, Serine, Mitogen-Activated Protein Kinases, Phosphorylation, Interleukin-1, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).1K popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 0.1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 0.1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 0.1%
Citations provided by BIP!Popularity provided by BIP!