title: Cytoplasmic truncation of the p55 tumour necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor.
abstract: The mechanistic relationship between the signalling for the TNF effects by the human p55 TNF receptor (hu-p55-TNF-R) and the formation of a soluble form of the receptor, which is inhibitory to these effects, was explored by examining the function of C-terminally truncated mutants of the receptor, expressed in rodent cells. The 'wild-type' receptor signalled for a cytocidal effect when cross-linked with specific antibodies and exhibited spontaneous shedding. Shedding of the receptor was not affected by TNF but was markedly enhanced by 4 beta-phorbol-12-myristate-13-acetate (PMA). Receptor mutants with 53%, 83% and 96% C-terminal deletions could not signal for the cytocidal effect. Furthermore, they were found to associate with the endogenous rodent receptors, interfering with their signalling. Yet even the deletion of 96% of the intracellular domain did not abolish shedding of the receptor in response to PMA. These findings suggest that signalling and shedding of the p55 TNF-R are mechanistically distinct.
authors.affiliation: Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: C
authors.initials: C
authors.lastname: Brakebusch
authors.forename: Y
authors.initials: Y
authors.lastname: Nophar
authors.forename: O
authors.initials: O
authors.lastname: Kemper
authors.forename: H
authors.initials: H
authors.lastname: Engelmann
authors.forename: D
authors.initials: D
authors.lastname: Wallach
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003432:Cross-Linking Reagents; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D013755:Tetradecanoylphorbol Acetate