Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1

Andrew R. Tee, John Blenis, Christopher G. Proud

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The small G protein Rheb (Ras homologue enriched in brain) is known to promote mammalian target of rapamycin (mTOR) signaling. In this study, we show that Rheb like-1 protein (RhebL1) rescues mTOR signaling during nutrient withdrawal and that tuberous sclerosis complex-1 (TSC) and TSC2 impairs RhebL1-mediated signaling through mTOR. We identify critical residues within the switch I region (N41) and 'constitutive' effector (Ec) region (Y/F54 and L56) of Rheb and RhebL1, which are required for their efficient activation of mTOR signaling. Mutation of Rheb and RhebL1 at N41 impaired their interaction with mTOR, which identifies mTOR as a common downstream target of both Rheb and RhebL1.

Original languageEnglish
Pages (from-to)4763-4768
Number of pages6
JournalFEBS Letters
Issue number21
Publication statusPublished - 29 Aug 2005
Externally publishedYes


  • 4E-BP1
  • Rheb
  • RhebL1
  • S6K1
  • TSC2
  • mTOR

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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