Identification of p55 tumor necrosis factor receptor-associated proteins that couple to signaling pathways not initiated by the death domain.
The 55 kDa receptor for tumor necrosis factor (TNF-R55) has become a paradigm for membrane receptors that are devoid of intrinsic enzymatic activity. The initiation of intracellular signaling events observed in TNF-stimulated cells appears to depend on protein intermediates that interact with specific cytoplasmic domains of TNF-R55. By use of TNF-R55 deletion mutants, we have defined a novel domain of TNF-R55 (NSD) distinct from the death domain which is specifically required for activation of neutral sphingomyelinase (N-SMase). In addition, using the yeast interaction trap system, we have identified one protein (FAN) that binds to the NSD and mediates activation of N-SMase as well as seventeen other potential interaction partners of TNF-R55. These candidate interactors include the adaptor protein Grb2-linking TNF-R55 to the Ras pathway-as well as the enzyme phosphoglycerate mutase, suggesting a role of TNF-R55 in glycolysis/ energy metabolism of cells.
Institut für Immunologie, Christian-Albrechts-Universität Kiel, Germany.
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Adam
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Adam-Klages
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Krönke
D000818:Animals; D017353:Gene Deletion; D051379:Mice; D010449:Peptide Mapping; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D047990:TNF Receptor-Associated Factor 1
D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047990:TNF Receptor-Associated Factor 1; D013108:Sphingomyelin Phosphodiesterase