title: RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs.
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.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: D M
authors.initials: DM
authors.lastname: Sabatini
authors.forename: H
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: M
authors.initials: M
authors.lastname: Lui
authors.forename: P
authors.initials: P
authors.lastname: Tempst
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D018076:DNA, Complementary / Q000032:analysis; D005656:Fungal Proteins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011090:Polyenes / Q000378:metabolism*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D020123:Sirolimus; D013388:Succinimides; D058570:TOR Serine-Threonine Kinases; D016559:Tacrolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D018076:DNA, Complementary; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011090:Polyenes; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; D013388:Succinimides; D058570:TOR Serine-Threonine Kinases; D016559:Tacrolimus; D022021:Tacrolimus Binding Proteins; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae; C019358:disuccinimidyl suberate