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. Act1 associates with and activates I kappa B kinase (IKK), leading to the liberation of NF-kappa B from its complex with I kappa B. Many signaling pathways that liberate NF-kappa B also activate activating transcription factor (ATF) and activator protein 1 (AP-1) through Jun kinase (JNK). Act1 also activates 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 activate NF-kappa B in an IL-1-unresponsive mutant cell line in which all known signaling components are present, suggesting that it interacts with an unknown component in IL-1 signaling.