Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38 - PubMed (original) (raw)
. 2007 Nov 9;318(5852):977-80.
doi: 10.1126/science.1147379.
Affiliations
- PMID: 17991864
- DOI: 10.1126/science.1147379
Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38
Xiaochun Bai et al. Science. 2007.
Abstract
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.
Comment in
- Cell signaling. mTOR, unleashed.
Proud CG. Proud CG. Science. 2007 Nov 9;318(5852):926-7. doi: 10.1126/science.1150653. Science. 2007. PMID: 17991850 No abstract available.
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