Overview:

NIK is a mitogen-activated protein kinase kinase kinase 14 (MAP3K14), which binds to TRAF2 and stimulates NF-kappaB activity. NIK shares sequence similarity with several other MAPKK kinases and participates in NF-kappaB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor. (1) NIK is expressed in primary human cells and in inflamed rheumatoid arthritis tissue and plays a selective role in signaling by the lymphotoxin-beta receptor (2). NIK is a therapeutic target in the immune and bone-destructive components of inflammatory arthritis.

References:

1. Smith, C. et.al: NF-kappa-B-inducing kinase is dispensable for activation of NF-kappa-B in inflammatory settings but essential for lymphotoxin beta receptor activation of NF-kappa-B in primary human fibroblasts. J. Immun. 167: 5895-5903, 2001.

2. Yin, L. et.al: Defective lymphotoxin-beta receptor-induced NF-kappa-B transcriptional activity in NIK-deficient mice. Science 291: 2162-2165, 2001.