Insights from vaccinia virus into Toll-like receptor signalling proteins and their regulation by ubiquitin: role of IRAK-2.
TLRs (Toll-like receptors) are an important class of pathogen-sensing proteins, which signal the presence of a pathogen by activating transcription factors, such as NF-kappaB (nuclear factor kappaB). The TLR pathway to NF-kappaB activation involves multiple phosphorylation and ubiquitination events. Notably, TRAF-6 [TNF (tumour necrosis factor)-receptor-associated factor-6] Lys(63) polyubiquitination is a critical step in the formation of signalling complexes, which turn on NF-kappaB. Here, the relative role of different IRAKs [IL-1 (interleukin 1)-receptor-associated kinases] in NF-kappaB activation is discussed. Further, I demonstrate how understanding one molecular mechanism whereby vaccinia virus inhibits NF-kappaB activation has led to a revealing of a key role for IRAK-2 in TRAF-6-mediated NF-kappaB activation.
Bowie
Andrew G
AG
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland. agbowie@tcd.ie
D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D014616:Vaccinia virus / Q000378:metabolism*
D051193:Toll-Like Receptors; D025801:Ubiquitin; D053592:Interleukin-1 Receptor-Associated Kinases