Gene interactions and pathways from curated databases and text-mining
Curr Biol 2005, PMID: 15854902

Rheb binds and regulates the mTOR kinase.

Long, Xiaomeng; Lin, Yenshou; Ortiz-Vega, Sara; Yonezawa, Kazuyoshi; Avruch, Joseph

BACKGROUND

The target of rapamycin (TOR), in complex with the proteins raptor and LST8 (TOR complex 1), phosphorylates the p70S6K and 4E-BP1 to promote mRNA translation. Genetic evidence establishes that TOR complex activity in vivo requires the small GTPase Rheb, and overexpression of Rheb can rescue TOR from inactivation in vivo by amino-acid withdrawal. The Tuberous Sclerosis heterodimer (TSC1/TSC2) functions as a Rheb GTPase activator and inhibits TOR signaling in vivo.

RESULTS

Here, we show that Rheb binds to the TOR complex specifically, independently of its ability to bind TSC2, through separate interactions with the mTOR catalytic domain and with LST8. Rheb binding to the TOR complex in vivo and in vitro does not require Rheb guanyl nucleotide charging but is modulated by GTP and impaired by certain mutations (Ile39Lys) in the switch 1 loop. Nucleotide-deficient Rheb mutants, although capable of binding mTOR in vivo and in vitro, are inhibitory in vivo, and the mTOR polypeptides that associate with nucleotide-deficient Rheb in vivo lack kinase activity in vitro. Reciprocally, mTOR polypeptides bound to Rheb(Gln64Leu), a mutant that is nearly 90% GTP charged, exhibit substantially higher protein kinase specific activity than mTOR bound to wild-type Rheb.

CONCLUSIONS

The TOR complex 1 is a direct target of Rheb-GTP, whose binding enables activation of the TOR kinase.

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Text Mining Data

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Manually curated Databases

  • IRef Bind Interaction: RPTOR — RHEB
  • IRef Bind Interaction: RHEB — ATR
  • IRef Bind Interaction: RHEB — MTOR
  • IRef Bind Interaction: RHEB — MLST8
  • IRef Bind Interaction: RHEB — TSC2
  • IRef Bind Interaction: RAF1 — RHEB
  • IRef Bind_translation Interaction: RPTOR — RHEB (affinity chromatography technology)
  • IRef Bind_translation Interaction: RHEB — ATR (affinity chromatography technology)
  • IRef Bind_translation Interaction: RHEB — MTOR (affinity chromatography technology)
  • IRef Bind_translation Interaction: MLST8 — RHEB (affinity chromatography technology)
  • IRef Bind_translation Interaction: RHEB — ATM (affinity chromatography technology)
  • IRef Bind_translation Interaction: RHEB — TSC2 (affinity chromatography technology)
  • IRef Bind_translation Interaction: RAF1 — RHEB (affinity chromatography technology)
  • IRef Biogrid Interaction: RHEB — RPTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RHEB — RPTOR (direct interaction, pull down)
  • IRef Biogrid Interaction: RHEB — ATR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RHEB — ATR (direct interaction, pull down)
  • IRef Biogrid Interaction: RAP1A — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RHEB — MTOR (direct interaction, pull down)
  • IRef Biogrid Interaction: RHEB — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RHEB — HRAS (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RHEB — RAP1A (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RPS6KB1 — MTOR (direct interaction, pull down)
  • IRef Biogrid Interaction: RHEB — ATM (direct interaction, pull down)
  • IRef Biogrid Interaction: RHEB — ATM (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: EIF4EBP1 — MTOR (direct interaction, pull down)
  • IRef Biogrid Interaction: RHEB — TSC2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RHEB — TSC2 (direct interaction, pull down)
  • IRef Biogrid Interaction: RAF1 — RHEB (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RAF1 — RHEB (direct interaction, pull down)
  • IRef Hprd Interaction: RHEB — ATR (in vitro)
  • IRef Hprd Interaction: RHEB — MTOR (in vivo)
  • IRef Hprd Interaction: RHEB — MTOR (in vitro)
  • IRef Hprd Interaction: RHEB — ATM (in vitro)
In total, 12 gene pairs are associated to this article in curated databases