J Biol Chem. 1999 Apr 9;274(15):10203-12.

Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling.External

Schutze, S., Machleidt, T., Adam, D., Schwandner, R., Wiegmann, K., Kruse, M. L., Heinrich, M., Wickel, M., Kronke, M.,
--- - Institute of Immunology, University of Kiel, 24105 Kiel, Germany. schuetze@immunologie.uni-kiel.de
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.
PMID: 10187805External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD TNFR1 Link TRADD Co-immunoprecipitation HEK293 Not used Not specified Not specified 10187805
(Link: click this icon to show interactions only between the two corresponding DDs)