Distinct differences between TNF receptor 1- and TNF receptor 2-mediated activation of NFkappaB.
Tumor necrosis factor (TNF) signaling is mediated via two distinct receptors, TNFR2 and TNFR1, which shows partially overlapping signaling mechanisms and biological roles. In the present study, TNFR2 and TNFR1 signal transduction mechanisms involved in activation of NFkappaB and CMV promoter-enhancer were compared with respect to their susceptibility towards inhibitors of intracellular signaling. For this, we used SW480 cells, where we have shown that TNF-signaling can occur independently through each of the two receptors. The TNFR1 response was inhibited by D609, bromophenacyl bromide (BPB), nordihydroguararetic acid (NDGA), and by sodium salicylate, while TNFR2-mediated activation of NFkappaB and CMV promoter-enhancer was resistant to these compounds. The signaling mechanisms known to be affected by these inhibitors include phospholipases as well as redox- and pH-sensitive intracellular components. Our results imply that TNFR2 signaling involved in NFkappaB activation proceeds independently of these inhibitor-sensitive signaling components, indicating distinct signaling pathways not shared with TNFR1.
Thommesen
Liv
L
Norwegian University of Science and Technology, Department of Cancer Research and Molecular Medicine, Sør-Trøndelag University College, Faculty of Technology, N-7489 Trondheim, Norway. liv.thommesen@medisin.ntnu.no
Laegreid
Astrid
A
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D003587:Cytomegalovirus / Q000235:genetics; D004742:Enhancer Elements, Genetic; D017930:Genes, Reporter; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000187:drug effects / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000187:drug effects / Q000502:physiology*; D012980:Sodium Salicylate / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D001616:beta-Galactosidase / Q000235:genetics
D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D001616:beta-Galactosidase; D013755:Tetradecanoylphorbol Acetate; D012980:Sodium Salicylate