An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways

J Biol Chem. 2000 Sep 8;275(36):27823-31. doi: 10.1074/jbc.M003415200.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Apoptosis
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Humans
  • I-kappa B Kinase
  • Mice
  • NF-kappa B / metabolism*
  • Nod1 Signaling Adaptor Protein
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Sequence Deletion
  • Signal Transduction / physiology
  • Transcription, Genetic*
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • NF-kappa B
  • NOD1 protein, human
  • Nod1 Signaling Adaptor Protein
  • Proteins
  • Protein Kinases
  • Protein Serine-Threonine Kinases
  • RIPK1 protein, human
  • RIPK2 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk1 protein, mouse
  • Ripk2 protein, mouse
  • CHUK protein, human
  • Chuk protein, mouse
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Ikbkb protein, mouse
  • Ikbke protein, mouse