The human toll signaling pathway: Divergence of nuclear factor κb and jnk/sapk activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6)

Abstract

The human homologue of Drosophila Toll (hToll) is a recently cloned receptor of the interleukin 1 receptor (IL-1R.) superfamily, and has been implicated in the activation of adaptive immunity. Signaling by hToll is shown to occur through sequential recruitment of the adapter molecule MyD88 and the IL-1R-associated kinase. Tumor necrosis factor receptor-activated factor 6 (TRAF6) and the nuclear factor κB (NF-κB)-inducing kinase (NIK) are both involved in subsequent steps of NF-κB activation. Conversely, a dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways.