Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38.
The mammalian target of rapamycin, mTOR, is a central regulator of cell growth. Its activity is regulated by Rheb, a Ras-like small guanosine triphosphatase (GTPase), in response to growth factor stimulation and nutrient availability. We show that Rheb regulates mTOR through FKBP38, a member of the FK506-binding protein (FKBP) family ... that is structurally related to FKBP12. FKBP38 binds to mTOR and inhibits its activity in a manner similar to that of the FKBP12-rapamycin complex. Rheb interacts directly with FKBP38 and prevents its association with mTOR in a guanosine 5'-triphosphate (GTP)-dependent manner. Our findings suggest that FKBP38 is an endogenous inhibitor of mTOR, whose inhibitory activity is antagonized by Rheb in response to growth factor stimulation and nutrient availability.
Mesh Terms:
Amino Acids, Cell Line, Culture Media, Guanosine Triphosphate, Humans, Insulin, Intercellular Signaling Peptides and Proteins, Monomeric GTP-Binding Proteins, Multiprotein Complexes, Mutant Proteins, Neuropeptides, Phosphorylation, Protein Binding, Protein Kinases, Protein Structure, Tertiary, Proteins, Recombinant Proteins, Serum, Signal Transduction, Sirolimus, TOR Serine-Threonine Kinases, Tacrolimus Binding Proteins, Transcription Factors
Amino Acids, Cell Line, Culture Media, Guanosine Triphosphate, Humans, Insulin, Intercellular Signaling Peptides and Proteins, Monomeric GTP-Binding Proteins, Multiprotein Complexes, Mutant Proteins, Neuropeptides, Phosphorylation, Protein Binding, Protein Kinases, Protein Structure, Tertiary, Proteins, Recombinant Proteins, Serum, Signal Transduction, Sirolimus, TOR Serine-Threonine Kinases, Tacrolimus Binding Proteins, Transcription Factors
Science
Date: Nov. 09, 2007
PubMed ID: 17991864
View in: Pubmed Google Scholar
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