Cross-linking of the p55 tumor necrosis factor receptor cytoplasmic domain by a dimeric ligand induces nuclear factor-kappa B and mediates cell death.
We have fused the cytoplasmic domain of the p55 tumor necrosis factor (TNF) receptor to the extracellular and transmembrane domain of the mouse platelet-derived growth factor (PDGF) receptor. Mouse mammary gland epithelial (NMuMG) cells were stably transfected with the PDGFR-TR55 chimeric receptor. These cells lack endogenous PDGF receptor expression and do not respond to PDGF. In the PDGFR-TR55 transfectants, PDGF elicited a cytotoxic response, which is indistinguishable from that induced by the wild type p55 TNF receptor. In addition, PDGF-induced activation of the PDGFR-TR55 chimeric receptor resulted in nuclear translocation of NF-kappa B. The data presented suggest that cross-linking of the p55 TNF receptor cytoplasmic domain by a dimeric ligand such as PDGF is sufficient to generate cellular responses that do not differ from those observed with the trimeric ligand TNF.
Adam
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D
Institut für Medizinische Mikrobiologie und Hygiene, Technische Universität München, Germany.
Kessler
U
U
Krönke
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M
D000818:Animals; D001483:Base Sequence; D016923:Cell Death; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016328:NF-kappa B; D010982:Platelet-Derived Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor