Gene interactions and pathways from curated databases and text-mining
J Immunol 2005, PMID: 15843522

IL-2 increases human telomerase reverse transcriptase activity transcriptionally and posttranslationally through phosphatidylinositol 3'-kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells.

Kawauchi, Kiyotaka; Ihjima, Kimiko; Yamada, Osamu

Human telomerase activity is induced by Ag receptor ligation in T and B cells. However, it is unknown whether telomerase activity is increased in association with activation and proliferation of NK cells. We found that telomerase activity in a human NK cell line (NK-92), which requires IL-2 for proliferation, was increased within 24 h after stimulation with IL-2. Levels of human telomerase reverse transcriptase (hTERT) mRNA and protein correlated with telomerase activity. ERK1/2 and Akt kinase (Akt) were activated by IL-2 stimulation. LY294002, an inhibitor of PI3K, abolished expression of hTERT mRNA and protein expression and abolished hTERT activity, whereas PD98059, which inhibits MEK1/2 and thus ERK1/2, had no effect. In addition, radicicol, an inhibitor of heat shock protein 90 (Hsp90), and rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), blocked IL-2-induced hTERT activity and nuclear translocation of hTERT but not hTERT mRNA expression. hTERT was coimmunoprecipitated with Akt, Hsp90, mTOR, and p70 S6 kinase (S6K), suggesting that these molecules form a physical complex. Immunoprecipitates of Akt, Hsp90, mTOR, and S6K from IL-2-stimulated NK-92 cells contained telomerase activity. Furthermore, the findings that Hsp90 and mTOR immunoprecipitates from primary samples contained telomerase activity are consistent with the results from NK-92 cells. These results indicate that IL-2 stimulation induces hTERT activation and that the mechanism of IL-2-induced hTERT activation involves transcriptional or posttranslational regulation through the pathway including PI3K/Akt, Hsp90, mTOR, and S6K in NK cells.

Diseases/Pathways annotated by Medline MESH: Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Lymphoid
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Text Mining Data

telomerase reverse transcriptase → IL-2: " IL-2 increases human telomerase reverse transcriptase activity transcriptionally and posttranslationally through phosphatidylinositol 3'-kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells "

3'-kinase/Akt → IL-2: " IL-2 increases human telomerase reverse transcriptase activity transcriptionally and posttranslationally through phosphatidylinositol 3'-kinase/Akt , heat shock protein 90, and mammalian target of rapamycin in transformed NK cells "

mammalian target of rapamycin → IL-2: " IL-2 increases human telomerase reverse transcriptase activity transcriptionally and posttranslationally through phosphatidylinositol 3'-kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells "

ERK1/2 → IL-2: " ERK1/2 and Akt kinase ( Akt ) were activated by IL-2 stimulation "

Akt kinase ( Akt ) → IL-2: " ERK1/2 and Akt kinase ( Akt ) were activated by IL-2 stimulation "

Manually curated Databases

  • IRef Biogrid Interaction: TERT — HSP90AA1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: AKT1 — HSP90AA1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: TERT — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: AKT1 — TERT (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: TERT — RPS6KB1 (physical association, affinity chromatography technology)
  • NCI Pathway Database Regulation of Telomerase: Erk1-2 (MAPK3/MAPK1) → Erk1-2-active (MAPK3/MAPK1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database Regulation of Telomerase: Erk1-2 (MAPK3/MAPK1) → IL2 (IL2) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: TERT (TERT) → Hsp90 (HSP90AA1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: TERT (TERT) → AKT1 (AKT1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: TERT (TERT) → AKT1/mTOR/p70S6K/Hsp90/TERT complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: TERT (TERT) → mTOR (MTOR) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: TERT (TERT) → p70S6K (RPS6KB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: Hsp90 (HSP90AA1) → AKT1 (AKT1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: Hsp90 (HSP90AA1) → AKT1/mTOR/p70S6K/Hsp90/TERT complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: Hsp90 (HSP90AA1) → mTOR (MTOR) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: Hsp90 (HSP90AA1) → p70S6K (RPS6KB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: AKT1 (AKT1) → AKT1/mTOR/p70S6K/Hsp90/TERT complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: AKT1 (AKT1) → mTOR (MTOR) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: AKT1 (AKT1) → p70S6K (RPS6KB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: AKT1/mTOR/p70S6K/Hsp90/TERT complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT) → mTOR (MTOR) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: AKT1/mTOR/p70S6K/Hsp90/TERT complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT) → p70S6K (RPS6KB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL2 signaling events mediated by PI3K: mTOR (MTOR) → p70S6K (RPS6KB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database Regulation of Telomerase: IL2 (IL2) → AKT1 (AKT1) (modification, activates)
    Evidence: assay
In total, 21 gene pairs are associated to this article in curated databases