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.
THE EXPRESSION OF THE NOD-2, CROHN'S DISEASE GENE, IS SPECIFIC FOR MONOCYTES (CERTAIN WHITE BLOOD CELLS). MAP IS KNOWN TO INFECT THESE WHITE BLOOD CELLS. THUS, ANY DEFECT IN THE NOD-2 GENE IN CD PATIENTS WOULD AFFECT THE WAY THE MONOCYTES FIGHT OFF A MAP INFECTION. THIS IS WHY NOT ALL PEOPLE EXPOSED TO MAP GET CROHN'S DISEASE. ONLY PEOPLE WITH DEFECTIVE BACTERIAL RESPONSE GENES AND ARE EXPOSED TO MAP GET CD. THIS IS ALSO USED AS AN ARGUMENT AGAINST THE MAP THEORY TO THE ETIOLOGY OF CD.
Source: http://www.crohns.org/articles/2001_02_4812-8_jbc.htm Contact PARA: http://www.crohns.org/contact.htm
Paratuberculosis Awareness & Research Association