Recombinant Human TWEAK/TNFSF12 Protein

TWEAK is a type II transmembrane protein belonging to the TNF superfamily (1). It contains a short cytoplasmic domain (aa 1‑18), the transmembrane domain
(aa 19-42) and an extracellular domain (aa 43-249). The extracellular domains of human and murine TWEAK share 89% aa sequence identity. A soluble form of TWEAK is generated from the membrane-associated molecules by proteolytic cleavage after Arg 93 suggesting that TWEAK may have long-range effects. TWEAK is expressed widely in many tissues and cells. At least two receptors that bind TWEAK have been identified (2-4). Death Receptor 3 (DR3), also known as TNFRSF12, Apo-3, LARD, WSL-1 or TRAMP, is a TNF receptor superfamily member that is expressed predominantly in tissues with high lymphocyte content (2). It has been suggested that induction of cell death by TWEAK-DR3 interaction involves the activation of NF-kappa B. In cells that lack DR3, alternate pathways of TWEAK-induced cell death mediated by receptors distinct from DR3 have been suggested (5, 6). TWEAK receptor (TWEAKR, alternatively known as FN14), is a novel TNF receptor superfamily member that also binds TWEAK (3, 4). It is a mitogen-inducible gene that is expressed in fibroblasts, hepetocellular carcinomas and endothelial cells. TWEAK-TWEAKR interaction has been shown to play a role in endothelial cell growth and migration. This effect of TWEAK is not mediated by an up-regulation of VEGF (7).