TUMOR-NECROSIS-FACTOR (TNF)-MEDIATED KINASE CASCADES - BIFURCATION OFNUCLEAR FACTOR-KAPPA-B AND C-JUN N-TERMINAL KINASE (JNK SAPK) PATHWAYS AT TNF RECEPTOR-ASSOCIATED FACTOR-2/

TNF-induced activation of the transcription factor NF-kappa B and the c-jun N-terminal kinase (JNK/SAPK) requires TNF receptor-associated fa ctor 2 (TRAF2). The NF-kappa B-inducing kinase (NIK) associates with T RAF2 and mediates TNF activation of NF-kappa B. Herein we show that NI K interacts with additional members of the TRAF family and that this i nteraction requires the conserved ''WKI'' motif within the TRAF domain . We also investigated the role of NIK in JNK activation by TNF. Where as overexpression of NIK potently induced NF-kappa B activation, it fa iled to stimulate JNK activation. A kinase-inactive mutant of NIK was a dominant negative inhibitor of NF-kappa B activation but did not sup press TNF-or TRAF2-induced JNK activation. Thus, TRAF2 is the bifurcat ion point of two kinase cascades leading to activation of NF-kappa B a nd JNK, respectively.