Several members of the tumour-necrosis/nerve-growth factor (TNF/NGF) r
eceptor family activate the transcription factor NF-kappa B through a
common adaptor protein, Traf2 (refs 1-5), whereas the interleukin 1 ty
pe-I receptor activates NF-kappa B independently of Traf2 (ref. 4). We
have now cloned a new protein kinase, NIK, which binds to Traf2 and s
timulates NF-kappa B activity. This kinase shares sequence similarity
with several MAPKK kinases. Expression in cells of kinase-deficient NI
K mutants fails to stimulate NF-kappa B and blocks its induction by TN
F, by either of the two TNF receptors or by the receptor CD95 (Fas/Apo
-1), and by TRADD, RIP and MORT1/FADD, which are adaptor proteins that
bind to these receptors. It also blocked NF-kappa B induction by inte
rleukin-l. Our findings indicate that NIK participates in an NF-kappa
B-inducing signalling cascade common to receptors of the TNF/NGF famil
y and to the interleukin-1 type-I receptor.