Gene interactions and pathways from curated databases and text-mining
Cell 2010, PMID: 20381137

Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids.

Sancak, Yasemin; Bar-Peled, Liron; Zoncu, Roberto; Markhard, Andrew L; Nada, Shigeyuki; Sabatini, David M

The mTORC1 kinase promotes growth in response to growth factors, energy levels, and amino acids, and its activity is often deregulated in disease. The Rag GTPases interact with mTORC1 and are proposed to activate it in response to amino acids by promoting mTORC1 translocation to a membrane-bound compartment that contains the mTORC1 activator, Rheb. We show that amino acids induce the movement of mTORC1 to lysosomal membranes, where the Rag proteins reside. A complex encoded by the MAPKSP1, ROBLD3, and c11orf59 genes, which we term Ragulator, interacts with the Rag GTPases, recruits them to lysosomes, and is essential for mTORC1 activation. Constitutive targeting of mTORC1 to the lysosomal surface is sufficient to render the mTORC1 pathway amino acid insensitive and independent of Rag and Ragulator, but not Rheb, function. Thus, Rag-Ragulator-mediated translocation of mTORC1 to lysosomal membranes is the key event in amino acid signaling to mTORC1.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

mTORC1 → Rag-Ragulator: " Thus, Rag-Ragulator mediated translocation of mTORC1 to lysosomal membranes is the key event in amino acid signaling to mTORC1 "

Manually curated Databases

  • Gene Ontology Complexes Ragulator complex: Ragulator complex complex (LAMTOR5-LAMTOR1-LAMTOR2-LAMTOR3)
  • IRef Intact Interaction: Complex of LAMTOR1-RRAGA-RRAGB-RRAGD-LAMTOR3-LAMTOR2 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: RRAGC — LAMTOR1 (colocalization, fluorescence microscopy)
  • IRef Intact Interaction: Complex of RRAGB-RRAGC-RRAGA (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of LAMTOR3-LAMTOR2-RRAGD-LAMTOR1 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of LAMTOR3-RRAGA-LAMTOR2-RRAGC (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of 11 proteins (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of RRAGB-RRAGB-LAMTOR3-LAMTOR2-LAMTOR1-LAMTOR3-LAMTOR2-LAMTOR1 (association, anti tag coimmunoprecipitation)
In total, 23 gene pairs are associated to this article in curated databases