Cytoplasmic truncation of the p55 tumour necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor.

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

SN - 0261-4189

VL - 11

SP - 943

EP - 950

JO - E M B O Journal

JF - E M B O Journal

IS - 3

ER -