Gene interactions and pathways from curated databases and text-mining
Science 2008, PMID: 18497260

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

Sancak, Yasemin; Peterson, Timothy R; Shaul, Yoav D; Lindquist, Robert A; Thoreen, Carson C; Bar-Peled, Liron; Sabatini, David M

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.

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Text Mining Data

mTORC1 ⊣ Rag: " Conversely, expression of a guanosine diphosphate bound Rag mutant prevented stimulation of mTORC1 by amino acids "

Manually curated Databases

  • IRef Biogrid Interaction: RRAGC — RPTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RRAGD — RPTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RRAGD — RPTOR (direct interaction, pull down)
  • IRef Biogrid Interaction: RAP2A — RPTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RRAGD — MTOR (direct interaction, pull down)
  • IRef Biogrid Interaction: RRAGD — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RRAGB — RPTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RRAGB — RPTOR (direct interaction, pull down)
  • IRef Biogrid Interaction: RRAGB — MTOR (direct interaction, pull down)
  • IRef Biogrid Interaction: RRAGD — RRAGB (direct interaction, pull down)
  • IRef Biogrid Interaction: RRAGD — RRAGB (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RRAGA — RPTOR (physical association, affinity chromatography technology)
  • NCI Pathway Database mTOR signaling pathway: RagA-B/GTP/RagC-D/GDP complex (RRAGA_RRAGB-RRAGC_RRAGD) → mTORC1/PRAS40/DEPTOR complex (MTOR-MLST8-AKT1S1-DEPTOR-RPTOR) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
In total, 35 gene pairs are associated to this article in curated databases