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Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB.

Apaf-1 and Nod1 are members of a protein family, each of which contains a caspase recruitment domain (CARD) linked to a nucleotide-binding domain, which regulate apoptosis and/or NF-kappaB activation. Nod2, a third member of the family, was identified. Nod2 is composed of two N-terminal CARDs, a nucleotide-binding domain, and multiple C-terminal leucine-rich repeats. Although Nod1 and Apaf-1 were broadly expressed in tissues, the expression of Nod2 was highly restricted to monocytes. Nod2 induced nuclear factor kappaB (NF-kappaB) activation, which required IKKgamma and was inhibited by dominant negative mutants of IkappaBalpha, IKKalpha, IKKbeta, and IKKgamma. Nod2 interacted with the serine-threonine kinase RICK via a homophilic CARD-CARD interaction. Furthermore, NF-kappaB activity induced by Nod2 correlated with its ability to interact with RICK and was specifically inhibited by a truncated mutant form of RICK containing its CARD. The identification of Nod2 defines a subfamily of Apaf-1-like proteins that function through RICK to activate a NF-kappaB signaling pathway.

Pubmed ID: 11087742


  • Ogura Y
  • Inohara N
  • Benito A
  • Chen FF
  • Yamaoka S
  • Nunez G


The Journal of biological chemistry

Publication Data

February 16, 2001

Associated Grants

  • Agency: NCI NIH HHS, Id: CA-64556

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Apoptotic Protease-Activating Factor 1
  • Carrier Proteins
  • Cell Line
  • Chromosomes, Human, Pair 16
  • Dimerization
  • Humans
  • I-kappa B Kinase
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Monocytes
  • Mutation
  • NF-kappa B
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Proteins
  • RNA, Messenger
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Sequence Homology, Amino Acid