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
February 16, 2001
- Agency: NCI NIH HHS, Id: CA-64556
- Adaptor Proteins, Signal Transducing
- Amino Acid Motifs
- Amino Acid Sequence
- Apoptotic Protease-Activating Factor 1
- Carrier Proteins
- Cell Line
- Chromosomes, Human, Pair 16
- I-kappa B Kinase
- Intracellular Signaling Peptides and Proteins
- Molecular Sequence Data
- NF-kappa B
- Nod1 Signaling Adaptor Protein
- Nod2 Signaling Adaptor Protein
- Protein Kinases
- Protein-Serine-Threonine Kinases
- RNA, Messenger
- Receptor-Interacting Protein Serine-Threonine Kinase 2
- Sequence Homology, Amino Acid
- Psoriatic arthritis, susceptibility to is related to genes NOD2, CARD15, IBD1, CD, ACUG, PSORAS1.
- Inflammatory bowel disease 1 is related to genes NOD2, CARD15, IBD1, CD, ACUG, PSORAS1 which are multifactorial according to the OMIM database.
- Blau syndrome is related to genes NOD2, CARD15, IBD1, CD, ACUG, PSORAS1 which are autosomal dominant according to the OMIM database.
- Sarcoidosis, early-onset is related to genes NOD2, CARD15, IBD1, CD, ACUG, PSORAS1.