Gene interactions and pathways from curated databases and text-mining
Cell 2012, PMID: 22980980

Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1.

Bar-Peled, Liron; Schweitzer, Lawrence D; Zoncu, Roberto; Sabatini, David M

The mTOR Complex 1 (mTORC1) pathway regulates cell growth in response to numerous cues, including amino acids, which promote mTORC1 translocation to the lysosomal surface, its site of activation. The heterodimeric RagA/B-RagC/D GTPases, the Ragulator complex that tethers the Rags to the lysosome, and the v-ATPase form a signaling system that is necessary for amino acid sensing by mTORC1. Amino acids stimulate the binding of guanosine triphosphate to RagA and RagB but the factors that regulate Rag nucleotide loading are unknown. Here, we identify HBXIP and C7orf59 as two additional Ragulator components that are required for mTORC1 activation by amino acids. The expanded Ragulator has nucleotide exchange activity toward RagA and RagB and interacts with the Rag heterodimers in an amino acid- and v-ATPase-dependent fashion. Thus, we provide mechanistic insight into how mTORC1 senses amino acids by identifying Ragulator as a guanine nucleotide exchange factor (GEF) for the Rag GTPases.

Document information provided by NCBI PubMed

Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • Gene Ontology Complexes Ragulator complex: Ragulator complex complex (LAMTOR5-LAMTOR1-LAMTOR2-LAMTOR3)
  • IRef Intact Interaction: LAMTOR3 — LAMTOR2 (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: LAMTOR4 — LAMTOR5 (physical association, affinity chromatography technology)
  • IRef Intact Interaction: Complex of LAMTOR4-LAMTOR3-LAMTOR1-RRAGC-RRAGA (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of LAMTOR4-MTOR-RPTOR (association, cross-linking study)
  • IRef Intact Interaction: Complex of RRAGB-LAMTOR3-RRAGC-LAMTOR1 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of LAMTOR2-MTOR-RPTOR (association, cross-linking study)
  • IRef Intact Interaction: LAMTOR5 — LAMTOR1 (colocalization, confocal microscopy)
  • IRef Intact Interaction: Complex of RPTOR-MTOR-LAMTOR1 (association, cross-linking study)
  • IRef Intact Interaction: Complex of LAMTOR1-RRAGA-LAMTOR3-RRAGC-LAMTOR2 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of RRAGA-RRAGC-LAMTOR2-RRAGC-LAMTOR2-RRAGA (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of LAMTOR5-RRAGC-LAMTOR3-LAMTOR1-LAMTOR2-LAMTOR4-RRAGB (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of 13 proteins (association, affinity chromatography technology)
  • IRef Intact Interaction: Complex of LAMTOR1-RRAGA-LAMTOR1-RRAGC-RRAGA-RRAGC (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: LAMTOR4 — LAMTOR1 (colocalization, confocal microscopy)
  • IRef Intact Interaction: Complex of RRAGA-RRAGC-LAMTOR5 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of 15 proteins (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of LAMTOR4-RRAGC-RRAGA (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of LAMTOR1-RRAGB-LAMTOR2 (association, affinity chromatography technology)
  • IRef Intact Interaction: Complex of RRAGB-LAMTOR2-LAMTOR3-LAMTOR5-LAMTOR1 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of MTOR-RPTOR-LAMTOR5 (association, cross-linking study)
  • IRef Intact Interaction: Complex of LAMTOR1-LAMTOR3-LAMTOR5-RRAGC-RRAGA (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of RRAGB-LAMTOR3-LAMTOR1 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of LAMTOR4-LAMTOR5-LAMTOR3-RRAGC-LAMTOR1-LAMTOR2 (association, affinity chromatography technology)
  • IRef Intact Interaction: Complex of RRAGA-ATP6V1B2-RRAGC-LAMTOR1 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: LAMTOR2 — RRAGB (physical association, affinity chromatography technology)
In total, 39 gene pairs are associated to this article in curated databases