Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38
X Bai, D Ma, A Liu, X Shen, QJ Wang, Y Liu, Y Jiang - Science, 2007 - science.org
X Bai, D Ma, A Liu, X Shen, QJ Wang, Y Liu, Y Jiang
Science, 2007•science.orgThe 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 …
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 …
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.
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