Froscio M, Murray A W, Hurst N P
Dept. of Medical Biochemistry, Flinders Medical Centre, Queen Elizabeth Hospital, Woodville, S. Australia.
Biochem Pharmacol. 1989 Jul 1;38(13):2087-9. doi: 10.1016/0006-2952(89)90061-0.
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.
钙离子激活的磷脂依赖性蛋白激酶（蛋白激酶C；PKC）在细胞外信号传递中起核心作用。口服活性抗风湿药物金诺芬已被证明可调节PKC介导的细胞反应。在本研究中，我们报告金诺芬以剂量依赖性方式直接抑制PKC；巯基乙醇可克服这种抑制作用。金诺芬还抑制蛋白水解激活的PKC，排除了该药物对酶调节域的影响。这些数据清楚地表明，金诺芬可能通过与巯基相互作用来抑制PKC的催化活性。
