Staphylococcus aureus α-toxin. 2. Reduction of epidermal growth factor receptor affinity in PC12 cells

P. Lazarovici and K. -F. J. Chan. Staphylococcus aureus α-toxin. 2. Reduction of epidermal growth factor receptor affinity in PC12 cells. Toxicon 25, 637 - 647 1987.-Staphylococcus aureus α-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 α-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 α-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 α-toxin has not been established, our results suggest that protein kinase C may be involved in this time-dependent process.