一种假定的西罗莫司（雷帕霉素）效应蛋白。

A putative sirolimus (rapamycin) effector protein.

作者信息

Chen Y, Chen H, Rhoad A E, Warner L, Caggiano T J, Failli A, Zhang H, Hsiao C L, Nakanishi K, Molnar-Kimber K L

机构信息

Department of Chemistry, Columbia University, New York, NY 10027.

出版信息

Biochem Biophys Res Commun. 1994 Aug 30;203(1):1-7. doi: 10.1006/bbrc.1994.2140.

DOI:10.1006/bbrc.1994.2140

PMID:7521160

Abstract

Sirolimus (rapamycin), a new immunosuppressive drug, inhibits proliferation of a wide spectrum of T and B cells. The immunosuppressive mechanism of sirolimus is still unclear. We recently isolated a membrane associated protein with an apparent molecular weight of 210 kDa, p210, from cultured Molt 4 cells and BJAB cells and from normal human T cells using an affinity matrix method. The p210 binds to sirolimus:FKBP12 complex, but only at background levels to FKBP12 alone, to FK506:FKBP12 complex, or sirolimus-biotin alone. Among the sirolimus analogs tested, the binding ability of p210 to drug:FKBP12 complexes correlates with the immunosuppressive activity of the drugs, suggesting that p210 is the sirolimus effector protein.

摘要

西罗莫司（雷帕霉素）是一种新型免疫抑制药物，可抑制多种T细胞和B细胞的增殖。西罗莫司的免疫抑制机制尚不清楚。我们最近使用亲和基质法从培养的Molt 4细胞、BJAB细胞以及正常人T细胞中分离出一种表观分子量为210 kDa的膜相关蛋白p210。p210可与西罗莫司：FKBP12复合物结合，但与单独的FKBP12、FK506：FKBP12复合物或单独的西罗莫司 - 生物素仅在背景水平结合。在所测试的西罗莫司类似物中，p210与药物：FKBP12复合物的结合能力与药物的免疫抑制活性相关，这表明p210是西罗莫司效应蛋白。