RAFT1：一种以雷帕霉素依赖方式与FKBP12结合且与酵母TORs同源的哺乳动物蛋白。

RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs.

作者信息

Sabatini D M, Erdjument-Bromage H, Lui M, Tempst P, Snyder S H

机构信息

Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

出版信息

Cell. 1994 Jul 15;78(1):35-43. doi: 10.1016/0092-8674(94)90570-3.

DOI:10.1016/0092-8674(94)90570-3

PMID:7518356

Abstract

The immunosuppressants rapamycin and FK506 bind to the same intracellular protein, the immunophilin FKBP12. The FKB12-FK506 complex interacts with and inhibits the Ca(2+)-activated protein phosphatase calcineurin. The target of the FKBP12-rapamycin complex has not yet been identified. We report that a protein complex containing 245 kDa and 35 kDa components, designated rapamycin and FKBP12 targets 1 and 2 (RAFT1 and RAFT2), interacts with FKBP12 in a rapamycin-dependent manner. Sequences (330 amino acids total) of tryptic peptides derived from the 245 kDa RAFT1 reveal striking homologies to the yeast TOR gene products, which were originally identified by mutations that confer rapamycin resistance in yeast. A RAFT1 cDNA was obtained and found to encode a 289 kDa protein (2549 amino acids) that is 43% and 39% identical to TOR2 and TOR1, respectively. We propose that RAFT1 is the direct target of FKBP12-rapamycin and a mammalian homolog of the TOR proteins.

摘要

免疫抑制剂雷帕霉素和FK506与同一细胞内蛋白亲免素FKBP12结合。FKB12 - FK506复合物与钙激活蛋白磷酸酶钙调神经磷酸酶相互作用并抑制其活性。FKBP12 - 雷帕霉素复合物的作用靶点尚未明确。我们报告称，一种含有245 kDa和35 kDa组分的蛋白复合物，命名为雷帕霉素和FKBP12靶点1和2（RAFT1和RAFT2），以雷帕霉素依赖的方式与FKBP12相互作用。源自245 kDa的RAFT1的胰蛋白酶肽段序列（共330个氨基酸）与酵母TOR基因产物具有显著同源性，酵母TOR基因产物最初是通过赋予酵母雷帕霉素抗性的突变鉴定出来的。获得了RAFT1的cDNA，发现其编码一种289 kDa的蛋白（2549个氨基酸），该蛋白与TOR2和TOR1的同源性分别为43%和39%。我们提出RAFT1是FKBP12 - 雷帕霉素的直接靶点以及TOR蛋白的哺乳动物同源物。