Reference: Sabatini DM, et al. (1995) The rapamycin and FKBP12 target (RAFT) displays phosphatidylinositol 4-kinase activity. J Biol Chem 270(36):20875-8

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Abstract


The immunosuppressant rapamycin prevents cell cycle progression in several mammalian cell lines and the yeast Saccharomyces cerevisiae. In mammalian cells, rapamycin binds to the small FK506-binding protein, FKBP12, allowing the drug-receptor complex to interact with the 289-kDa RAFT1/FRAP proteins. These proteins, along with their yeast homologs, TOR1/DRR1 and TOR2/DRR2, contain a C-terminal domain with amino acid homology to several phosphatidylinositol (PI) 4- and 3-kinases. However, no direct demonstration of kinase activity for this family of proteins has been reported. We now show that RAFT1, immunoprecipitated from rat brain and MG63 and HEK293 cells, contains PI 4-kinase activity and that rapamycin-FKBP12 has no effect on this activity. Thus, it is likely that, in vivo, rapamycin does not directly inhibit the PI 4-kinase activity and affects the RAFT1/FRAP protein through another mechanism.

Reference Type
Journal Article | Research Support, U.S. Gov't, P.H.S.
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Sabatini DM, Pierchala BA, Barrow RK, Schell MJ, Snyder SH
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