RAFT1 - A MAMMALIAN PROTEIN THAT BINDS TO FKBP12 IN A RAPAMYCIN-DEPENDENT FASHION AND IS HOMOLOGOUS TO YEAST TORS
RAFT1 - A MAMMALIAN PROTEIN THAT BINDS TO FKBP12 IN A RAPAMYCIN-DEPENDENT FASHION AND IS HOMOLOGOUS TO YEAST TORS
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DOI：
10.1016/0092-8674(94)90570-3
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发表时间：
1994-07-15
期刊：
影响因子：
64.5
通讯作者：
SNYDER, SH
中科院分区：
文献类型：
--
作者：
SABATINI, DM;ERDJUMENTBROMAGE, H;SNYDER, SH
免疫抑制剂雷帕霉素和FK 506结合相同的细胞内蛋白，亲免素FKBP 12。FKBP 12-FK 506复合物与Ca 2+激活的蛋白磷酸酶钙调磷酸酶相互作用并抑制钙调磷酸酶。FKBP 12-雷帕霉素复合物的靶点尚未确定。我们报告了一种蛋白质复合物，含有245 kDa和35 kDa的组件，指定雷帕霉素和FKBP 12的目标1和2（RAFT 1和RAFT 2），与FKBP 12相互作用的雷帕霉素依赖性的方式。来自245 kDa RAFT 1的胰蛋白酶肽序列（共330个氨基酸）显示与酵母TOR基因产物具有惊人的同源性，该基因产物最初通过赋予酵母中雷帕霉素抗性的突变来鉴定。RAFT 1 cDNA获得，并发现编码一个289 kDa的蛋白质（2549个氨基酸），这是43%和39%相同的TOR 2和TOR 1，分别。我们认为RAFT 1是FKBP 12-雷帕霉素的直接靶点，也是TOR蛋白的哺乳动物同源物。
The immunosuppressants rapamycin and FK506 bind to the same intracellular protein, the immunophilin FKBP12. The FKBP12-FK506 complex interacts with and inhibits the Ca2+-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.