title: Biological activities of human tumor necrosis factor-alpha and its novel mutants.
abstract: Biological activities of human tumor necrosis factor-alpha (hTNF-alpha) and its mutants were compared. In cytotoxicity assay with L929 cells, one mutant, designated as TNF-B, showed 4.5-fold higher activity than TNF examined. In receptor binding assay, TNF-B had almost the same affinity for TNF receptors on L929 cells as hTNF-alpha. We also found that TNF-B retained the cytotoxicity of hTNF-alpha for HEp-2 cells. TNF-B also had two-fold higher affinity than hTNF-alpha for receptors on HEp-2 cells (only carrying hTNF-R55) and lower affinity for receptors on U937 cells (expressing mainly hTNF-R75). These results suggested that TNF-B might still interact with the human TNF-R55 receptor, but it might largely lose its ability to bind to human TNF-R75. Changes of biological activity of TNFs might be due to an altered affinity to the different types of TNF receptor on the target cells.
authors: Department of Biochemistry, Nanjing University, People's Republic of China.
authors: T
authors: T
authors: Xi
authors: X
authors: X
authors: Shi
authors: D
authors: D
authors: Guo
authors: X
authors: X
authors: Dong
authors: X
authors: X
authors: Xu
authors: D
authors: D
authors: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011869:Radioligand Assay; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha