TNFR2 Signalling Regulation By Novel TRAF2-binding Site

Thu, 02/18/2010 - 09:14

Tumour Necrosis Factor Receptor 2 (TNFR2) exists as both a cytoplasmic and transmembrane glycoprotein. Together with TNFR1, it has been shown to stimulate T lymphocyte activity via TNFα action. The TNF signalling pathways are complex, and mutation or disruption of the proteins at any stage can cause oncogenesis. Therefore TNF-related antibodies are widely used in immunoassays for cancer research.

TNF receptor proteins activate the TRAF2 signal transduction protein at the T2bs-N binding site at their cytoplasmic domain, stimulating NF kappa B and JNK activation. However, TNFR2 has been shown to be a poor signalling pathway activator, despite having a high affinity for TRAF2.

Western Blot: TNF Receptor II Antibody Western Blot: TNF Receptor II Antibody

In 2005, new studies showed that TNFR2 links to T2bs-C, a novel carboxyl-terminal TRAF2-binding site which blocks activation signals released from its T2bs-N binding site. Using IHC antibody-binding and other assays, it was shown that T2bs-C does not follow the orthodox pattern of TRAF2 binding action, and it was suggested binding of TRAF2 happened indirectly, via a third intermediary. Inactivation of T2bs-N by mutation led to depletion of most of the TRAF2 at the cytoplasmic domain. However, the activation of the NF kappa B and JNK pathways, which are ligand-dependent, was unaffected.

In contrast, T2bs-C inactivation had minimum effect on the take-up of TRAF2, but significantly increased the rate of NF-kB and JNK activation. It was therefore suggested that T2bs-C activates signalling by dominating the more active T2bs-N, rather than by preventing TRAF2 activation. The conclusion was that this mechanism allows TNFR2 to regulate TNFR1-induced signalling.

Research is constantly uncovering new cell signalling proteins. It is up to people like us at Novus Biologicals to develop the relevant antibodies that enable such research to continue.

Novus Biologicals offers many TNF Receptor II reagents for your research needs including:


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