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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.

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.

Pubmed ID: 15843522


  • Kawauchi K
  • Ihjima K
  • Yamada O


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

May 1, 2005

Associated Grants


Mesh Terms

  • Cell Line, Transformed
  • Chromones
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Extracellular Signal-Regulated MAP Kinases
  • Flavonoids
  • HSP90 Heat-Shock Proteins
  • Humans
  • Interleukin-2
  • Killer Cells, Natural
  • Lactones
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphocyte Activation
  • Macrolides
  • Morpholines
  • Phosphatidylinositol 3-Kinases
  • Protein Kinases
  • Protein Processing, Post-Translational
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • RNA-Directed DNA Polymerase
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Sirolimus
  • TOR Serine-Threonine Kinases
  • Telomerase
  • Transcription, Genetic