Ligand passing: the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor.
To understand the role of the 75-kDa tumor necrosis factor (TNF) receptor in non-lymphoid cells, the cytotoxic signaling and ligand binding activities of the 55-kDa (TNF-R1) and 75-kDa (TNF-R2) TNF receptors were investigated using agonist and antagonist antibodies specific for the two receptor types. This study indicates that although TNF-R2 can significantly reduce the TNF concentration required for cell killing, the mechanism by which this is accomplished is not through the generation of an intracellular signal by TNF-R2. Instead, TNF-R2 regulates the rate of TNF association with TNF-R1, possibly by increasing the local concentration of TNF at the cell surface through rapid ligand association and dissociation. We propose that other cell-surface receptors, such as the low affinity p75 nerve growth factor receptor, may utilize an analogous "ligand passing" mechanism.
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.
L A
LA
Tartaglia
D
D
Pennica
D V
DV
Goeddel
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal; D016923:Cell Death; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D011956:Receptors, Cell Surface / Q000276:immunology / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha