Terada N, Lucas J J, Szepesi A, Franklin R A, Takase K, Gelfand E W
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Biochem Biophys Res Commun. 1992 Aug 14;186(3):1315-21. doi: 10.1016/s0006-291x(05)81549-9.
Phosphorylation of 40S ribosomal protein S6 is regulated in part by the mitogen-activated p70 S6 kinase (p70s6k). Following the addition of IL-2 to the IL-2 dependent human cell line Kit225, or mitogenic activation of resting human T cells, a rapid phosphorylation of p70s6k was observed by immunoblotting. Rapamycin (RAP), a potent suppressor of T-cell proliferative responses, markedly inhibited the phosphorylation of p70s6k induced by IL-2 in Kit225 cells or by the mitogens added to resting T cells. Other immunosuppressants such as cyclosporin A or an FK506 analogue were without effect. Moreover, the effect of RAP was restricted to p70s6k; it did not inhibit the phosphorylation of p90rsk, another kinase which utilizes the S6 protein as a substrate. These data indicate for the first time that RAP may target the pathway leading to p70s6k phosphorylation during human T-cell proliferation.
40S核糖体蛋白S6的磷酸化部分受有丝分裂原激活的p70 S6激酶（p70s6k）调控。将白细胞介素-2（IL-2）添加到依赖IL-2的人细胞系Kit225中，或使静息的人T细胞发生有丝分裂原激活后，通过免疫印迹观察到p70s6k迅速磷酸化。雷帕霉素（RAP）是T细胞增殖反应的强效抑制剂，它显著抑制了IL-2在Kit225细胞中或添加到静息T细胞中的有丝分裂原所诱导的p70s6k磷酸化。其他免疫抑制剂如环孢素A或FK506类似物则无此作用。此外，RAP的作用仅限于p70s6k；它并不抑制p90rsk的磷酸化，p90rsk是另一种以S6蛋白为底物的激酶。这些数据首次表明，RAP可能在人T细胞增殖过程中靶向导致p70s6k磷酸化的途径。
