Cytoplasmic truncation of the p55 tumour necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor.
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Cytoplasmic truncation of the p55 tumour necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor. / Brakebusch, C; Nophar, Y; Kemper, O; Engelmann, H; Wallach, D.
In: EMBO Journal, Vol. 11, No. 3, 1992, p. 943-50.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cytoplasmic truncation of the p55 tumour necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor.
AU - Brakebusch, C
AU - Nophar, Y
AU - Kemper, O
AU - Engelmann, H
AU - Wallach, D
N1 - Keywords: 3T3 Cells; Animals; Antibodies, Monoclonal; Base Sequence; Cell Survival; Cricetinae; Cross-Linking Reagents; Cytoplasm; DNA; Electrophoresis, Polyacrylamide Gel; Gene Expression; Hela Cells; Humans; Mice; Molecular Sequence Data; Receptors, Cell Surface; Receptors, Tumor Necrosis Factor; Signal Transduction; Tetradecanoylphorbol Acetate; Transfection; Tumor Necrosis Factor-alpha
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 1312466
VL - 11
SP - 943
EP - 950
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 3
ER -
ID: 5160432