Staphylococcus aureus alpha-toxin. 2. Reduction of epidermal growth factor receptor affinity in PC12 cells.
Staphylococcus aureus alpha-toxin, at sub-cytotoxic concentrations, inhibits both the 125I-labeled epidermal growth factor (EGF) binding and autophosphorylation properties of EGF-receptors in PC12 cells. This inhibition occurred only in intact cells and is probably due to a decrease in the affinity of the receptor for EGF. Streptolysin S and parcelsin could mimic the alpha-toxin effect below cytotoxic concentrations, as measured by a 51Cr release assay. In contrast, other membrane perturbing toxins with different lipid specificity, such as tetanolysin and cobra direct lytic factor, inhibited [125I]EGF binding only at cytotoxic concentrations. Staphylococcal alpha-toxin also stimulated 3-fold the specific binding of a radioactive tumor-promoting phorbol ester (PDBu) to PC12 cells at concentrations similar to those required for the inhibition of [125I]EGF binding. Although the exact mechanism for the inhibition of EGF binding by alpha-toxin has not been established, our results suggest that protein kinase C may be involved in this time-dependent process.
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006460:Hemolysin Proteins; D007457:Iodine Radioisotopes; D008564:Membrane Potentials / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
D001427:Bacterial Toxins; D003432:Cross-Linking Reagents; D006460:Hemolysin Proteins; D007457:Iodine Radioisotopes; C021091:staphylococcal alpha-toxin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C