The biology and biochemistry of inflammatory signalosomes

Abstract

The Juan March Foundation symposium on Signaling Networks in Immunity and Inflammation took place in Madrid, Spain, between 22 and 24 May 2005 and was organized by J. Moscat, M. Karin, P. Rennert and C. Martinez‐A. ![][1] This two‐day workshop on inflammatory signalling was the first Juan March Foundation symposium to be held at the new Cantoblanco campus of the University Autonomous of Madrid. The intimate audience and the breadth of material discussed made for an exciting and highly interactive meeting. Fuelled by excellent wine and strong coffee, scientific conversations continued late into the night after dinner in Madrid's beautiful plazas. The prominent and long‐recognized role of the nuclear factor‐κB (NF‐κB) cascade in inflammatory responses made this pathway a main focus of the meeting. However, emerging paradigms in innate signalling receptors and their effectors—including the Toll‐like, Nacht‐leucine‐rich repeats (NLR) and p53‐induced protein with a death domain (PIDD) receptor systems—and the myriad events that are required to fine‐tune the adaptive immune response, from interchromosomal interaction to specific co‐receptors and effectors, also received significant attention. In this report, I attempt to highlight several new concepts related to these inflammatory signalling cascades. ### Initiation and modulation of NF‐κB signalling The meeting began with an introduction by I. Verma (San Diego, CA, USA) of the events mediating the NF‐κB cascade. The evolutionarily conserved, core NF‐κB signalling module is comprised of five NF‐κB/Rel family transcription factors, five potential IκB family regulatory subunits and three IκB kinases (IKKs)—including the catalytically active subunits IKKα and β, as well as the catalytically inactive, co‐associated regulatory subunit IKKγ (also known as NEMO; Fig 1; reviewed in Hayden & Ghosh, 2004). Figure 1. Members of the nuclear factor‐κB, IκB and IκB kinase families. The number of amino acids in each protein is indicated (right). Cleavage sites for p100, p105 and selected phosphorylation and ubiquitylation sites are shown. NF‐κB, … [1]: /embed/graphic-1.gif