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Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3)
A Kaptein1, M Jansen, G Dilaver
1Cell Biology Department, GlaxoWellcome Medicines Research Centre, Stevenage, UK.
Abstract:
WSL-1/TRAMP (DR3) is a member of the tumour necrosis factor (TNF) receptor superfamily which exhibits effects on NF-kappaB activation and apoptosis. TWEAK, a novel TNF-related molecule, has been proposed as the ligand for this receptor. Utilising both human and murine TWEAK ligand, it is shown that TWEAK and WSL-1/TRAMP do not interact in an in vitro binding assay and that TWEAK binds strongly to cells that do not express WSL-1/TRAMP on the cell surface. Biological activity of TWEAK is also observed in these cells. Finally, cells isolated from WSL-1/TRAMP knockout mice are shown to retain their ability to interact with TWEAK. These results suggest that WSL-1/TRAMP is not the major receptor for TWEAK
Insights
Tumor Necrosis Factor (TNF) receptor superfamily member WSL-1/TRAMP (DR3) does not bind TWEAK. These findings indicate WSL-1/TRAMP is not the primary receptor for the novel TNF-related molecule TWEAK.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- WSL-1/TRAMP (DR3) is a TNF receptor superfamily member involved in NF-kappaB activation and apoptosis.
- TWEAK, a novel TNF-related molecule, has been hypothesized as the ligand for WSL-1/TRAMP.
Purpose of the Study:
- To investigate the interaction between TWEAK and its putative receptor WSL-1/TRAMP.
- To determine if WSL-1/TRAMP is the major receptor for TWEAK.
Main Methods:
- In vitro binding assays using human and murine TWEAK ligands.
- Cell-based assays to assess TWEAK binding and biological activity on cells with and without WSL-1/TRAMP expression.
- Analysis of TWEAK interaction with cells from WSL-1/TRAMP knockout mice.
Main Results:
- TWEAK did not interact with WSL-1/TRAMP in in vitro binding assays.
- TWEAK bound strongly to cells lacking WSL-1/TRAMP surface expression, with observed biological activity.
- Cells from WSL-1/TRAMP knockout mice retained the ability to interact with TWEAK.
Conclusions:
- WSL-1/TRAMP is not the major receptor for TWEAK.
- The findings challenge the proposed ligand-receptor relationship between TWEAK and WSL-1/TRAMP.