Editors' ChoicemTOR Signaling

Regulating the Regulators

Science's STKE  13 Nov 2007:
Vol. 2007, Issue 412, pp. tw418
DOI: 10.1126/stke.4122007tw418

Growth factors and nutrients, particularly amino acids, regulate cell growth and proliferation in part through the serine-threonine protein kinase mTOR (mammalian target of rapamycin). Activity of mTOR is regulated through the small guanosine triphosphatase Rheb (Ras homolog enriched in brain). Bai et al. (see the Perspective by Proud) reveal a mechanism by which Rheb could control activity of mTOR. The protein FKBP38 binds to mTOR and inhibits its kinase activity. Active GTP-bound Rheb can interact with FKBP38 and thereby free mTOR from inhibition. This process may represent a critical control mechanism whose altered function is associated with human diseases, including cancer.

X. Bai, D. Ma, A. Liu, X. Shen, Q. J. Wang, Y. Liu, Y. Jiang, Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38. Science 318, 977-980 (2007). [Abstract] [Full Text]

C. G. Proud, mTOR, unleashed. Science 318, 926-927 (2007). [Summary] [Full Text]