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GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR.

mTOR and raptor are components of a signaling pathway that regulates mammalian cell growth in response to nutrients and growth factors. Here, we identify a member of this pathway, a protein named GbetaL that binds to the kinase domain of mTOR and stabilizes the interaction of raptor with mTOR. Like mTOR and raptor, GbetaL participates in nutrient- and growth factor-mediated signaling to S6K1, a downstream effector of mTOR, and in the control of cell size. The binding of GbetaL to mTOR strongly stimulates the kinase activity of mTOR toward S6K1 and 4E-BP1, an effect reversed by the stable interaction of raptor with mTOR. Interestingly, nutrients and rapamycin regulate the association between mTOR and raptor only in complexes that also contain GbetaL. Thus, we propose that the opposing effects on mTOR activity of the GbetaL- and raptor-mediated interactions regulate the mTOR pathway.

Pubmed ID: 12718876

Authors

  • Kim DH
  • Sarbassov DD
  • Ali SM
  • Latek RR
  • Guntur KV
  • Erdjument-Bromage H
  • Tempst P
  • Sabatini DM

Journal

Molecular cell

Publication Data

April 29, 2003

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI47389

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Base Sequence
  • Carrier Proteins
  • Cell Differentiation
  • Cell Size
  • Eukaryotic Cells
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • Molecular Sequence Data
  • Phosphoproteins
  • Protein Binding
  • Protein Kinases
  • Protein Structure, Tertiary
  • Protein Subunits
  • Proteins
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Signal Transduction
  • Sirolimus
  • TOR Serine-Threonine Kinases
  • Tacrolimus Binding Proteins