Enhancement of Protein Kinase C-mediated EGF Receptor Phosphorylation by Auranofin

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Abstract
The lipophilic anti-inflammatory and immunoregulatory gold (I) complex, 2,3,4,6-tetra-O-acetyl-l-thio-β-D-glucopyranosato-S-[triethylphosphine] gold (auranofin) is now widely used in the treatment of rheumatoid arthritis (1). Although the specific biochemical action(s) of auranofin are not known, the drug has been shown to react readily with thiol groups (2). Such interactions may alter the activity of key enzymes either by direct involvement with the catalytic site or through allosteric effects. Several reports have indicated that auranofin can modulate cellular activation responses which involve the Ca2+-activated, phospholipid-dependent protein kinase (PKC). For example, low concentrations of auranofin (< 1 μM) enhance–and higher concentrations inhibit–the production of superoxide in neutrophils incubated with phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA), a known activator of PKC (3).