Inhibition of receptor internalization by monodansylcadaverine selectivelyblocks p55 tumor necrosis factor receptor death domain signaling

The 55-kDa receptor for tumor necrosis factor (TR55) triggers multiple sign aling cascades initiated by adapter proteins like TRADD and FAN. By use of the primary amine monodansylcadaverine (MDC), we addressed the functional r ole of tumor necrosis factor (TNF) receptor internalization for intracellul ar signal distribution, We show that MDC does not prevent the interaction o f the p55 TNF receptor (TR55) with FAN and TRADD, Furthermore, the activati on of plasmamembrane-associated neutral sphingomyelinase activation as well as the stimulation of proline-directed protein kinases were not affected i n 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 s uggest a role of TR55 internalization for the activation of select TR55 dea th domain signaling pathways including those leading to apoptosis.