Human 55-kDa receptor for tumor necrosis factor coupled to signal transduction cascades.
The numerous biological activities of tumor necrosis factor (TNF) appear mediated by two types of receptors of 55 kDa (TR55) and 75 kDa (TR75) molecular mass. To test TR55 for its individual role in signaling across the membrane, a cDNA coding for the human TR55 was stably expressed in murine 70Z/3 pre-B cells, which lack binding sites for, and proved nonresponsive to human TNF. The transfected TR55 showed high affinity ligand binding and active internalization. It is demonstrated that the TNF signaling cascade, i.e. stimulation of protein kinase C, sphingomyelinase, and phospholipase A2, production of the second messengers diacylglycerol and ceramide, can occur completely through exclusive binding of TNF to TR55. The p55 TNF-binding site functions as an autonomous TNF receptor that mediates key signal transduction pathways, which may control the majority of TNF actions.
Wiegmann
K
K
Institut für Medizinische Mikrobiologie und Hygiene, Technische Universität München, Federal Republic of Germany.
Schütze
S
S
Kampen
E
E
Himmler
A
A
Machleidt
T
T
Krönke
M
M
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007700:Kinetics; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000378:metabolism; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D002518:Ceramides; D004075:Diglycerides; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2