Table of Contents
How is the NF-kB pathway activated?
The primary mechanism for canonical NF-κB activation is the inducible degradation of IκBα triggered through its site-specific phosphorylation by a multi-subunit IκB kinase (IKK) complex. IKK is composed of two catalytic subunits, IKKα and IKKβ, and a regulatory subunit named NF-κB essential modulator (NEMO) or IKKγ.
What is NF-κB signaling pathway?
Nuclear factor kappa B (NF-κB) is an ancient protein transcription factor (Salminen et al., 2008) and considered a regulator of innate immunity (Baltimore, 2009). The NF-κB signaling pathway links pathogenic signals and cellular danger signals thus organizing cellular resistance to invading pathogens.
What is NF kappaB and what is its role in mediating signals through TLRS?
All TLR signaling pathways culminate in activation of the transcription factor nuclear factor-kappaB (NF-κB), which controls the expression of an array of inflammatory cytokine genes.
Where does NF KB bind to?
Further studies demonstrated that NF-κB binds to DNA as a dimer that is formed by the combination of several proteins that contain an N-terminal Rel homology domain, which is responsible for NF-κB DNA binding and dimerization.
How does TNF alpha activate Nfkb?
TNF family signaling to NF-κB involves binding of a series of adapter proteins to the ligand bound receptor complex, which in turn recruits and activates IKK.
What cytokines does NF KB induce?
NF-κB mediates the induction of pro-inflammatory cytokines, such as TNF-α, IL-1 and IL-6, in monocytes/macrophages.
What is the best way to quantify NF-κB nuclear translocation?
Fluorescence microscopy, laser scanning cytometry and flow cytometry to quantify NF-κB nuclear translocation have all been reported (Deptala et al., 1998; George et al., 2006; Rogers and Fuseler, 2007; Fuseler et al., 2006). Drawbacks of these previous reports are the need for expensive imaging equipment and/or image analysis software.
What is the role of IKK in the NF-κB response to antigens?
The latter is a component of the NF-κB response to antigens in T cells (Thome and Tschopp 2002). Interestingly, IKK-mediated Bcl10 phosphorylation induces its degradation, resulting in down-regulation of NF-κB signaling (Lobry et al. 2007).
Does TAK1 interfere with the IKK and JNK pathway?
Indeed it has been shown that TAK1, which is also an upstream kinase for the JNK pathway, can phosphorylate IKKβ in the activation loop, that its down-regulation interferes with IKK activation, and that mutations in the TAK1 gene in Drosophilainterfere with the NF-κB and JNK pathways (Vidal et al. 2001; Silverman et al. 2003).
Does IKKα need to be phosphorylated to activate IKKβ?
Although phosphorylation of IKKβ is necessary for activation of the canonical pathway, phosphorylation of IKKα is not, though it is required for activation of the alternative pathway. As is often the case, the identity of the phosphatases that deactivate the kinases is relatively unclear.