Regulation of the TNF-alpha receptor in human osteosarcoma cells: role of microtubules and of protein kinase C.
The effect of the tumor promoter 4 beta-phorbol 12-myristate 13-acetate and of the phosphatases inhibitor okadaic acid on the binding of tumor necrosis factor-alpha (TNF-alpha) to a human osteogenic sarcoma cell line (Saos-2) was investigated. Both substances prevented almost completely TNF binding to its receptors. The effect of 4 beta-phorbol 12-myristate 13-acetate was reversed by the protein kinase C inhibitors staurosporine and calphostin C or by protein kinase C depletion. Vinblastine, under conditions causing full microtubule disassembly, produced only a 50% decrease of TNF binding. Vinblastine plus PMA was additive in fully preventing TNF binding. It is suggested that the degree of binding of TNF-alpha to its receptors in Saos-2 cells is under the control of a microtubule-dependent and of a microtubule-independent regulatory pathway.
Galeotti
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Institut für Biochemie und Molekularbiologie, Universität Bern, Switzerland.
Boscoboinik
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Azzi
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D000470:Alkaloids / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D009281:Naphthalenes; D019319:Okadaic Acid; D012516:Osteosarcoma; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology*
D000470:Alkaloids; D004988:Ethers, Cyclic; D009281:Naphthalenes; D011083:Polycyclic Compounds; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019319:Okadaic Acid; D014747:Vinblastine; D003513:Cycloheximide; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate