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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain Chemistry
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Cloning, Molecular
  • Cross-Linking Reagents
  • DNA, Complementary / analysis
  • Fungal Proteins / genetics
  • Heat-Shock Proteins / isolation & purification
  • Heat-Shock Proteins / metabolism*
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Polyenes / metabolism*
  • Rats
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins*
  • Sequence Alignment
  • Sequence Analysis
  • Sequence Homology, Amino Acid
  • Sirolimus
  • Succinimides
  • TOR Serine-Threonine Kinases
  • Tacrolimus / metabolism
  • Tacrolimus Binding Proteins

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Cross-Linking Reagents
  • DNA, Complementary
  • Fungal Proteins
  • Heat-Shock Proteins
  • Polyenes
  • Saccharomyces cerevisiae Proteins
  • Succinimides
  • Phosphotransferases (Alcohol Group Acceptor)
  • TOR1 protein, S cerevisiae
  • TOR2 protein, S cerevisiae
  • TOR Serine-Threonine Kinases
  • Tacrolimus Binding Proteins
  • disuccinimidyl suberate
  • Sirolimus
  • Tacrolimus

Associated data

  • GENBANK/U11681