Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2006, PMID: 16798736

Activation of mammalian target of rapamycin (mTOR) by insulin is associated with stimulation of 4EBP1 binding to dimeric mTOR complex 1.

Wang, Lifu; Rhodes, Christopher J; Lawrence, John C

Insulin stimulates protein synthesis by promoting phosphorylation of the eIF4E-binding protein, 4EBP1. This effect is rapamycin-sensitive and mediated by mammalian target of rapamycin (mTOR) complex 1 (mTORC1), a signaling complex containing mTOR, raptor, and mLST8. Here we demonstrate that insulin produces a stable increase in the kinase activity of mTORC1 in 3T3-L1 adipocytes. The response was associated with a marked increase in 4EBP1 binding to raptor in mTORC1, and it was abolished by disrupting the TOR signaling motif in 4EBP1. The stimulatory effects of insulin on both 4EBP1 kinase activity and binding occurred rapidly and at physiological concentrations of insulin, and both effects required an intact mTORC1. Results of experiments involving size exclusion chromatography and coimmunoprecipitation of epitope-tagged subunits provide evidence that the major insulin-responsive form is dimeric mTORC1, a structure containing two heterotrimers of mTOR, raptor, and mLST8.

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Text Mining Data

mammalian target of rapamycin (mTOR) → insulin: " Activation of mammalian target of rapamycin (mTOR) by insulin is associated with stimulation of 4EBP1 binding to dimeric mTOR complex 1 "

4EBP1 → Insulin: " Insulin stimulates protein synthesis by promoting phosphorylation of the eIF4E binding protein, 4EBP1 "

mTORC1 → insulin: " Here we demonstrate that insulin produces a stable increase in the kinase activity of mTORC1 in 3T3-L1 adipocytes "

mTORC1 → 4EBP1: " The stimulatory effects of insulin on both 4EBP1 kinase activity and binding occurred rapidly and at physiological concentrations of insulin, and both effects required an intact mTORC1 "

mTORC1 → insulin: " The stimulatory effects of insulin on both 4EBP1 kinase activity and binding occurred rapidly and at physiological concentrations of insulin, and both effects required an intact mTORC1 "

4EBP1 — insulin: " The stimulatory effects of insulin on both 4EBP1 kinase activity and binding occurred rapidly and at physiological concentrations of insulin, and both effects required an intact mTORC1 "

Manually curated Databases

  • IRef Biogrid Interaction: MLST8 — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: LRPAP1 — EIF4EBP1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: MLST8 — RPTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF4EBP2 — MTOR (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: RPTOR — EIF4E (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF4EBP1 — EIF4E (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RPTOR — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: LRPAP1 — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF4EBP1 — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF4EBP1 — MTOR (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: EIF4EBP1 — RPTOR (physical association, affinity chromatography technology)
In total, 10 gene pairs are associated to this article in curated databases