Use of an NF-kappa B-dependent selectable marker facilitated the isolation
of a cell line containing a cDNA encoding Act1, an NF-kappa B activator. Ac
t1 associates with and activates I kappa B kinase (IKK), leading to the lib
eration of NF-kappa B from its complex with I kappa B. Many signaling pathw
ays that liberate NF-kappa B also activate activating transcription factor
(ATF) and activator protein 1 (AP-1) through Jun kinase (JNK). Act1 also ac
tivates JNK, suggesting that it might be part of a multifunctional complex
involved in the activation of both NF-kappa B and JNK. Act1 fails to activa
te NF-kappa B in an IL-1-unresponsive mutant cell line in which all known s
ignaling components are present, suggesting that it interacts with an unkno
wn component in IL-1 signaling.