• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1.

The multiprotein mTORC1 protein kinase complex is the central component of a pathway that promotes growth in response to insulin, energy levels, and amino acids and is deregulated in common cancers. We find that the Rag proteins--a family of four related small guanosine triphosphatases (GTPases)--interact with mTORC1 in an amino acid-sensitive manner and are necessary for the activation of the mTORC1 pathway by amino acids. A Rag mutant that is constitutively bound to guanosine triphosphate interacted strongly with mTORC1, and its expression within cells made the mTORC1 pathway resistant to amino acid deprivation. Conversely, expression of a guanosine diphosphate-bound Rag mutant prevented stimulation of mTORC1 by amino acids. The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb.

Pubmed ID: 18497260

Authors

  • Sancak Y
  • Peterson TR
  • Shaul YD
  • Lindquist RA
  • Thoreen CC
  • Bar-Peled L
  • Sabatini DM

Journal

Science (New York, N.Y.)

Publication Data

June 13, 2008

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI47389
  • Agency: NIAID NIH HHS, Id: R01 AI047389
  • Agency: NIAID NIH HHS, Id: R01 AI047389-09
  • Agency: NCI NIH HHS, Id: R01 CA103866
  • Agency: NCI NIH HHS, Id: R01 CA103866
  • Agency: NCI NIH HHS, Id: R01 CA103866-05

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acids
  • Cell Line
  • Cell Nucleus
  • Cytoplasm
  • Dimerization
  • Guanosine Triphosphate
  • Humans
  • Insulin
  • Leucine
  • Monomeric GTP-Binding Proteins
  • Multiprotein Complexes
  • Mutant Proteins
  • Mutation
  • Neuropeptides
  • Phosphorylation
  • Protein Binding
  • Protein Kinases
  • Proteins
  • Signal Transduction
  • TOR Serine-Threonine Kinases
  • Transcription Factors