A novel p75TNF receptor isoform mediating NF kappa B activation

We report the identification of a novel p75TNF receptor isoform termed icp7 5TNFR, which is generated by the use of an alternative transcriptional star t site within the p75TNFR gene and characterized by regulated intracellular expression. The icp75TNFR protein has an apparent molecular mass of simila r to 50 kDa and is recognized by antibodies generated against the transmemb rane form of p75TNFR. The icp75TNFR binds the tumor necrosis factor(TNF) an d mediates intracellular signaling. Overexpression of the icp75TNFR cDNA re sults in TNF-induced activation of NF kappaB in a TNF receptor-associated f actor 2 (TRAF2)-dependent manner. Thus, our results provide an example for intracellular cytokine receptor activation.