TNFR and LTBR signaling pathways for NFKB activation

TNFR and LTβR signaling pathways for NFκB activation. Signaling through TNFR activates the canonical RelA NFκB pathway, which involves the α, β and γ (NEMO) subunits of the IκB kinase (IKK) complex, which leads to proteosomal degradation of IκB, releasing RelA/p50 dimer from its cytoplasmic constraint, locate to the nucleus and binding κB transcriptional target sequences. LTβR ligation activates the serine kinases NIK and IKKα (also a part of the canonical pathway). The phosphorylation and ubiquitin-dependent proteasomal degradation of p100 results in the processing of the precursor to the p52 subunit and accumulation of p52-RelB heterodimers to the nucleus. Signaling through the LTβR also leads to the activation of the classical NF-κB pathway. TNFR signaling rapidly activates a large number of proinflammatory genes, whereas LTβR activation of RelB takes several hours but sustained expression in the nucleus leads to different sets of activated genes involved in homeostasis, such as the chemokine, CCL21.

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The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis. () Carl De Trez, et al. Cytokine Growth Factor Rev. ;19(3-4):277-284. Figure: F3. Homo sapiens

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