TRAF2 plays a dual role in NF-κB-dependent gene activation by mediating the TNF-induced activation of p38 MAPK and IκB kinase pathways

We previously demonstrated that p38 MAPK is a crucial mediator in the NF-kappa B-dependent gene activation induced by TNF. Here, we have studied the role of several TNF receptor-associated proteins and caspases in p38 MAPK activation by TNF. The latter appears to be dependent on TRAF2, but independent of FADD or caspases. Remarkably, p38 MARK activation by TNF proceeds independently of the TRAF2-associated NF-kappa B-inducing kinase NIK, which is known to bind and activate two recently identified I kappa B kinases. These results demonstrate that two kinase pathways involved in NF-kappa B regulation, viz, NIK and p38 MAPK-mediated, diverge at the level of TRAF2. (C) 1998 Federation of European Biochemical Societies.