CD27, A MEMBER OF THE TUMOR-NECROSIS-FACTOR RECEPTOR SUPERFAMILY, ACTIVATES NF-KB AND STRESS-ACTIVATED PROTEIN KINASE C-JUN N-TERMINAL KINASE VIA TRAF2, TRAF5, AND NF-KB-INDUCING KINASE/

CD27 is a member of the tumor necrosis factor (TNF) receptor superfami ly and is expressed on T, B, and NK cells. The signal via CD27 plays p ivotal roles in T-T and T-B cell interactions. Here we demonstrate tha t overexpression of CD27 activates NF-kappa B and stress-activated pro tein kinase (SAPK)/c-Jun N-terminal kinase (JNK). Deletion analysis of the cytoplasmic domain of CD27 revealed that the C-terminal PIQEDYR m otif was indispensable for both NF-kappa B and SAPK/JNK activation and was also required for the interaction with TNF receptor-associated fa ctor (TRAF) 2 and TRAF5, both of which have been implicated in NF-kapp a B activation by members of the TNF-R superfamily. Co-transfection of a dominant negative TRAF2 or TRAF5 blocked NF-kappa B and SAPK/JNK ac tivation induced by CD27. Recently, a TRAF2-interacting kinase has bee n identified, termed NF-kappa B-inducing kinase (NIK). A kinase-inacti ve mutant NIK blocked CD27-, TRAF2-, and TRAF5-mediated NF-kappa B and SAPK/JNK activation. These results indicate that TRAF2 and TRAF5 are involved in NF-kappa B and SAPK/JNK JNK activation by CD27, and MK is a common downstream kinase of TRAF2 and TRAF5 for NF-kappa B and SAPK/ JNK activation.