The Human Toll Signaling Pathway: Divergence of Nuclear Factor κB and JNK/SAPK Activation Upstream of Tumor Necrosis Factor Receptor–associated Factor 6 (TRAF6)

• DOI: 10.1084/jem.187.12.2097
• Publication Date: 2002-07-26T16:49:30Z
• Authors: Marta Muzio; Gioacchino Natoli; Simona Saccani; Massimo Levrero; Alberto Mantovani
• Keywords: Interleukin-1 receptor

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