Tumor Necrosis Factor (TNF) Receptor 1 Signaling Downstream of TNF Receptor-associated Factor 2 NUCLEAR FACTOR κB (NFκB)-INDUCING KINASE REQUIREMENT FOR ACTIVATION OF ACTIVATING PROTEIN 1 AND NFκB BUT NOT OF c-Jun N-TERMINAL KINASE/STRESS-ACTIVATED PROTEIN KINASE

摘要: Like other members of the tumor necrosis factor (TNF) receptor family, p55 TNF 1 (TNF-R1) lacks intrinsic signaling capacity and transduces signals by recruiting associating molecules. The TNF-R1 associated death domain protein interacts with cytoplasmic recruits Fas-associated (which directly activates apoptotic proteases), kinase interacting protein, receptor-associated 2 (TRAF2). TRAF2 has previously been demonstrated to activate both transcription nuclear kappaB (NFkappaB) c-Jun N-terminal kinase/stress-activated (JNK/SAPK) pathway, which in turn stimulates activating (AP1) mainly via phosphorylation component. We have investigated properties NFkappaB-inducing (NIK), a TRAF2-associated that mediates NFkappaB induction. NIK was found be unable JNK/SAPK, mitogen-activated kinase, or p38 kinase. Moreover, not required for JNK/SAPK activation TNF-R1, thus representing first complex component dissect pathways. Despite being strongly activated AP1 TNF-R1-induced activation. Therefore, links novel, JNK/SAPK-independent, pathway.