An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways.
Nod1 is an Apaf-1-like molecule composed of a caspase-recruitment domain (CARD), nucleotide-binding domain, and leucine-rich repeats that associates with the CARD-containing kinase RICK and activates nuclear factor kappaB (NF-kappaB). We show that self-association of Nod1 mediates proximity of RICK and the interaction of RICK with the gamma subunit of the IkappaB kinase (IKKgamma). Similarly, the RICK-related kinase RIP associated via its intermediate region with IKKgamma. A mutant form of IKKgamma deficient in binding to IKKalpha and IKKbeta inhibited NF-kappaB activation induced by RICK or RIP. Enforced oligomerization of RICK or RIP as well as of IKKgamma, IKKalpha, or IKKbeta was sufficient for induction of NF-kappaB activation. Thus, the proximity of RICK, RIP, and IKK complexes may play an important role for NF-kappaB activation during Nod1 oligomerization or trimerization of the tumor necrosis factor alpha receptor.
Pubmed ID: 10880512 RIS Download
Adaptor Proteins, Signal Transducing | Animals | Apoptosis | Carrier Proteins | Cell Line | Fibroblasts | Humans | I-kappa B Kinase | Mice | NF-kappa B | Nod1 Signaling Adaptor Protein | Protein Kinases | Protein-Serine-Threonine Kinases | Proteins | Receptor-Interacting Protein Serine-Threonine Kinase 2 | Receptor-Interacting Protein Serine-Threonine Kinases | Sequence Deletion | Signal Transduction | Transcription, Genetic | Transfection