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A mammalian protein targeted by G1-arresting rapamycin-receptor complex.
- Source :
-
Nature [Nature] 1994 Jun 30; Vol. 369 (6483), pp. 756-8. - Publication Year :
- 1994
-
Abstract
- The structurally related natural products rapamycin and FK506 bind to the same intracellular receptor, FKBP12, yet the resulting complexes interfere with distinct signalling pathways. FKBP12-rapamycin inhibits progression through the G1 phase of the cell cycle in osteosarcoma, liver and T cells as well as in yeast, and interferes with mitogenic signalling pathways that are involved in G1 progression, namely with activation of the protein p70S6k (refs 5, 11-13) and cyclin-dependent kinases. Here we isolate a mammalian FKBP-rapamycin-associated protein (FRAP) whose binding to structural variants of rapamycin complexed to FKBP12 correlates with the ability of these ligands to inhibit cell-cycle progression. Peptide sequences from purified bovine FRAP were used to isolate a human cDNA clone that is highly related to the DRR1/TOR1 and DRR2/TOR2 gene products from Saccharomyces cerevisiae. Although it has not been previously demonstrated that either of the DRR/TOR gene products can bind the FKBP-rapamycin complex directly, these yeast genes have been genetically linked to a rapamycin-sensitive pathway and are thought to encode lipid kinases.
- Subjects :
- Amino Acid Sequence
Animals
Carrier Proteins analysis
Carrier Proteins chemistry
Carrier Proteins genetics
Cattle
Cell Cycle Proteins
Cell Line
Cloning, Molecular
DNA, Complementary
Fungal Proteins genetics
Humans
Molecular Sequence Data
Phosphotransferases (Alcohol Group Acceptor) genetics
Polyenes pharmacology
Proteins chemistry
Proteins genetics
Recombinant Fusion Proteins genetics
Saccharomyces cerevisiae genetics
Sequence Homology, Amino Acid
Sirolimus
TOR Serine-Threonine Kinases
Tacrolimus Binding Proteins
Carrier Proteins metabolism
G1 Phase drug effects
Heat-Shock Proteins metabolism
Immunophilins
Phosphatidylinositol 3-Kinases
Polyenes metabolism
Proteins analysis
Saccharomyces cerevisiae Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0028-0836
- Volume :
- 369
- Issue :
- 6483
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 8008069
- Full Text :
- https://doi.org/10.1038/369756a0