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

@article{Sabatini1994RAFT1AM,
  title={RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs},
  author={David M. Sabatini and Hediye Erdjument-Bromage and Mary Lui and Paul Tempst and Solomon H. Snyder},
  journal={Cell},
  year={1994},
  volume={78},
  pages={35-43}
}
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… Expand
The Rapamycin and FKBP12 Target (RAFT) Displays Phosphatidylinositol 4-Kinase Activity (*)
TLDR
It is shown 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. Expand
Mammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast.
TLDR
Findings directly link the mammalian TOR homolog RAFT1 to rapamycin action in vivo and indicate that the TOR/RAFT1 kinase domain has been functionally conserved from yeast to man. Expand
RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex.
  • M. I. Chiu, H. Katz, V. Berlin
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1994
TLDR
Using a two-hybrid system, mammalian clones that interact with the human FK506/rapamycin-binding protein (FKBP12) in the presence of rapamycin are isolated and specific interactors, designated RAPT1, encode overlapping sequences homologous to yeast Tor, a putative novel phosphatidylinositol 3-kinase. Expand
FAP48, a New Protein That Forms Specific Complexes with Both Immunophilins FKBP59 and FKBP12
TLDR
The results suggest that FAP48 shares or overlaps the macrolide binding site on FKBP59 as well as on FkBP12 and therefore may represent a natural common ligand of these immunosuppressant drug receptors. Expand
Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells (*)
TLDR
The results strongly suggest that the FKBP12-rapamycin complex interacts with homologous ligands in yeast and mammalian cells and that the loss of mTOR function is directly related to the inhibitory effect of rapamycin on G1- to S-phase progression in T-lymphocytes and other sensitive cell types. Expand
Hmo1p, a high mobility group 1/2 homolog, genetically and physically interacts with the yeast FKBP12 prolyl isomerase.
TLDR
This work finds that mutations in HMO1, which encodes a high mobility group 1/2 homolog, are synthetically lethal with mutations in the yeast FPR1 gene encoding FKBP12, and suggests that FkBP12-HMG1/2 interactions could represent the first conserved function of FK BP12 other than mediating FK506 and rapamycin actions. Expand
Protein kinase activity and identification of a toxic effector domain of the target of rapamycin TOR proteins in yeast.
TLDR
The findings identify a toxic effector domain of the TOR proteins that may interact with substrates or regulators of theTOR kinase cascade and that shares sequence identity with other PIK family members, including ATR, Rad3, Mei-41, and ATM. Expand
The immunophilin FKBP65 forms an association with the serine/threonine kinase c-Raf-1.
TLDR
It is shown that the heat shock protein hsp90 and the serine/threonine protein kinase c-Raf-1 are components of FKBP65 immune complexes. Expand
The FKBP12-Rapamycin-binding Domain Is Required for FKBP12-Rapamycin-associated Protein Kinase Activity and G1 Progression*
TLDR
A model for FRAP function is proposed, in which the FRB domain is required for activation of the kinase domain, possibly through the interaction with an upstream activator, and direct evidence linking FRB function to G1 cell cycle progression is provided. Expand
The yeast FKS1 gene encodes a novel membrane protein, mutations in which confer FK506 and cyclosporin A hypersensitivity and calcineurin-dependent growth.
TLDR
Genomic disruption experiments suggest that FKS1 provides a unique cellular function which, when absent, increases FK506 and CsA sensitivity by making the CNs (or a CN-dependent function) essential. Expand
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References

SHOWING 1-10 OF 63 REFERENCES
Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases
TLDR
These studies identify a rapamycin-sensitive signaling pathway, argue for a ubiquitous role for FKBPs in signal transduction, indicate that FK506-FKBP-calcineurin complexes do not interfere with pp70S6K signaling, and show that in fibroblasts pp70 S6K, not RSK, is the physiological S6 kinase. Expand
Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity.
TLDR
Genomic disruption of DRR1 in a mutant haploid strain restored drug sensitivity and demonstrated that the gene encodes a nonessential function, which supports the idea that FKBP12 and rapamycin form a toxic complex that corrupts the function of other cellular proteins. Expand
Rapamycin-FKBP12 blocks proliferation, induces differentiation, and inhibits cdc2 kinase activity in a myogenic cell line.
TLDR
It is reported that rapamycin also blocks myogenic proliferation and induces differentiation, associated with a decrease in p34cdc2 activity and cyclin A levels, and identifies a regulatory step during myogenic differentiation. Expand
Molecular cloning of a 25-kDa high affinity rapamycin binding protein, FKBP25.
TLDR
The molecular cloning and overexpression of a 25-kDa rapamycin and FK506 binding protein with peptidylprolyl cis-trans-isomerase (PPIase) activity is reported and it is demonstrated that FKBP25 has a higher affinity forRapamycin than forFK506 and suggested that this cellular receptor may be an important target molecule for immunosuppression by rapamcin. Expand
Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast
TLDR
Nonallelic noncomplementation between FPR1, TOR1, and TOR2 alleles suggests that the products of these genes may interact as subunits of a protein complex that may mediate nuclear entry of signals required for progression through the cell cycle. Expand
TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast.
TLDR
TOR1 and TOR2 are likely similar but not identical, rapamycin-sensitive PI kinases possibly regulated by phosphorylation, and may be components of a novel signal transduction pathway controlling progression through G1. Expand
Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression.
TLDR
Yeast genetic studies suggest that the FKBP-rapamycin target is a protein complex involved in cell cycle progression, and further studies should provide fundamental insights into T-cell activation, signal transduction, and protein folding, and hold the promise of more specific immunosuppressive therapies. Expand
FKBP-rapamycin inhibits a cyclin-dependent kinase activity and a cyclin D1-Cdk association in early G1 of an osteosarcoma cell line.
TLDR
It is reported that rapamycin can be added 4 to 6 h after the addition of serum growth factors to quiescent human osteosarcoma cells and still arrest these cells in G1, and it is demonstrated that FKBP-rapamycinCan modulate a cyclin-dependent kinase activity and a Cyclin D1-cdk association during early G1 in MG-63 human osteoarthritis cells. Expand
Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression
TLDR
The results suggest that 3-phosphorylated phosphoinositides, whose physiological significance has not been determined, are an important signal in cell cycle activation in yeast and may act in a signalTransduction pathway similar to the interleukin-2 signal transduction pathway in T cells. Expand
A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin
CYCLOSPORIN A and the newly discovered immunosuppressant, FK-506, are potent inhibitors of T cell activation1. In addition to their clinical importance in the prevention of allograft rejection,Expand
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