Tollip Blooms in IL-1 Receptor Pathway

Abstract

The interleukin 1 (IL-1) receptor (IL-1R) activates a proinflammatory response through the activation of several signaling proteins and the transcription factors AP-1 and NF-κB. Burns et al . have molecularly cloned Tollip, an adapter protein involved in IL-1R signaling. In transfected cells, Tollip was shown to exist in a complex with the IL-1R-associated serine/threonine kinase (IRAK) before activation by IL-1. Upon stimulation with IL-1, the Tollip-IRAK complex associated with the IL-1R accessory protein (IL-1RAcP). However, activation of IRAK by another IL-1R-associated protein, MyD88, led to the dissociation of IRAK from Tollip, suggesting that IRAK dissociation is phosphorylation-dependent. Overexpression of Tollip led to decreased activation of NF-κB and JNK1. It is uncertain whether this represents a physiological effect of Tollip or reflects occlusion of limiting IL-1R binding sites for Tollip-IRAK complexes. Burns, K., Clatworthy, J., Martin, L., Martinon, F., Plumpton, C., Maschera, B., Lewis, A., Ray, K., Tschopp, J., and Volpe, F. (2000) Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nature Cell Biol . 2 : 346-351. [Online Journal]