Inhibition of protein kinase C activity by the antirheumatic drug auranofin.

The Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C; PKC) has a central role in the transmission of extracellular signals. The orally active anti-rheumatic drug, auranofin, has been shown to modulate PKC-mediated cell responses. In this study, we report that auranofin directly inhibits PKC in a dose-dependent manner; inhibition can be overcome by mercapto-ethanol. Proteolytically-activated PKC is also inhibited by auranofin excluding an effect of the drug on the regulatory domain of the enzyme. These data clearly show that auranofin inhibits the catalytic activity of PKC, probably by interacting with thiol groups.