Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling.
The 55-kDa receptor for tumor necrosis factor (TR55) triggers multiple signaling cascades initiated by adapter proteins like TRADD and FAN. By use of the primary amine monodansylcadaverine (MDC), we addressed the functional role of tumor necrosis factor (TNF) receptor internalization for intracellular signal distribution. We show that MDC does not prevent the interaction of the p55 TNF receptor (TR55) with FAN and TRADD. Furthermore, the activation of plasmamembrane-associated neutral sphingomyelinase activation as well as the stimulation of proline-directed protein kinases were not affected in MDC-treated cells. In contrast, activation of signaling enzymes that are linked to the "death domain" of TR55, like acid sphingomyelinase and c-Jun-N-terminal protein kinase as well as TNF signaling of apoptosis in U937 and L929 cells, are blocked in the presence of MDC. The results of our study suggest a role of TR55 internalization for the activation of select TR55 death domain signaling pathways including those leading to apoptosis.
Schütze
S
S
Institute of Immunology, University of Kiel, 24105 Kiel, Germany. schuetze@immunologie.uni-kiel.de
Machleidt
T
T
Adam
D
D
Schwandner
R
R
Wiegmann
K
K
Kruse
M L
ML
Heinrich
M
M
Wickel
M
M
Krönke
M
M
D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D002103:Cadaverine / Q000031:analogs & derivatives* / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D020928:Mitogen-Activated Protein Kinases; D011188:Potassium / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D047990:TNF Receptor-Associated Factor 1; D020298:U937 Cells; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D002518:Ceramides; D047908:Intracellular Signaling Peptides and Proteins; C102036:NSMAF protein, human; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047990:TNF Receptor-Associated Factor 1; D019014:fas Receptor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D013108:Sphingomyelin Phosphodiesterase; C008542:monodansylcadaverine; D002103:Cadaverine; D011188:Potassium