Price D J, Grove J R, Calvo V, Avruch J, Bierer B E
Diabetes Unit, Massachusetts General Hospital, Boston.
Science. 1992 Aug 14;257(5072):973-7. doi: 10.1126/science.1380182.
The immunosuppressant rapamycin inhibited proliferation of the H4IIEC hepatoma cell line. Rapamycin, but not its structural analog FK506, also inhibited the basal and insulin-stimulated activity of the p70 ribosomal protein S6 kinase. By contrast, insulin stimulation of the p85 Rsk S6 kinase and mitogen-activated protein (MAP) kinase activity were unaffected by drug. Rapamycin treatment of COS cells transfected with recombinant p70 S6 kinase completely inhibited the appearance of the hyperphosphorylated form of p70 S6 kinase concomitant with the inhibition of enzyme activity toward 40S subunits. Thus, rapamycin inhibits a signal transduction element that is necessary for the activation of p70 S6 kinase and mitogenesis but unnecessary for activation of p85 Rsk S6 kinase or MAP kinase.
免疫抑制剂雷帕霉素抑制H4IIEC肝癌细胞系的增殖。雷帕霉素而非其结构类似物FK506，也抑制p70核糖体蛋白S6激酶的基础活性及胰岛素刺激的活性。相比之下，胰岛素对p85 Rsk S6激酶的刺激及丝裂原活化蛋白（MAP）激酶活性不受该药物影响。用重组p70 S6激酶转染COS细胞后进行雷帕霉素处理，完全抑制了p70 S6激酶超磷酸化形式的出现，同时抑制了该酶对40S亚基的活性。因此，雷帕霉素抑制了一个信号转导元件，该元件对于p70 S6激酶的激活和有丝分裂是必需的，但对于p85 Rsk S6激酶或MAP激酶的激活并非必需。
