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J Biol Chem. 2001 Feb 16;276(7):4812-8. Epub 2000 Nov 21.

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

Author information

1
Department of Pathology and Comprehensive Cancer Center, the University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Abstract

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.

PMID:
11087742
DOI:
10.1074/jbc.M008072200
[Indexed for MEDLINE]
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