RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs.
Level 5 - mechanism / opinion, no new human data
In vitro bench and molecular characterization without clinical or in vivo human data
PubMed 7518356 · doi:10.1016/0092-8674(94)90570-3
What was done
The authors isolated mammalian proteins that interact with the immunophilin FKBP12 in the presence of rapamycin. They obtained tryptic peptide sequences (330 amino acids total) from the isolated 245 kDa protein component (designated RAFT1), cloned the full-length RAFT1 cDNA, and analyzed its sequence homology against yeast TOR proteins.
What was found
FKBP12 interacted in a rapamycin-dependent manner with a protein complex containing 245 kDa (RAFT1) and 35 kDa (RAFT2) components. The cloned RAFT1 cDNA encoded a 2,549-amino-acid protein with a predicted molecular mass of 289 kDa. The RAFT1 amino acid sequence exhibited 43% identity to yeast TOR2 and 39% identity to yeast TOR1.
Why it matters
This study identified RAFT1 (now commonly known as mTOR) as the direct mammalian target of the FKBP12-rapamycin complex, establishing that the target of rapamycin signaling pathway is structurally conserved from yeast to mammals.
Limits
The study is limited to in vitro biochemical purification and sequence homology analysis. The abstract reports no in vivo functional assays, downstream signaling mechanisms, or characterization of the 35 kDa RAFT2 component.
Cited by
- supports Rapamycin inhibits a protein complex centered on the mammalian target of rapamycin (mTOR), a discovery made by David Sabatini as a PhD student at Johns Hopkins in 1993–1994.