Gene interactions and pathways from curated databases and text-mining
Proc Natl Acad Sci U S A 2001, PMID: 11134523

A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt.

Aoki, M; Blazek, E; Vogt, P K

The oncoproteins P3k (homolog of the catalytic subunit of class IA phosphoinositide 3-kinase) and Akt (protein kinase B) induce oncogenic transformation of chicken embryo fibroblasts. The transformed cells show constitutive phosphorylation of the positive regulator of translation p70S6 kinase (S6K) and of the eukaryotic initiation factor 4E-BP1 binding protein (4E-BP1), a negative regulator of translation. Phosphorylation activates S6K and inactivates 4E-BP1. A mutant of Akt that retains kinase activity but does not induce phosphorylation of S6K or of 4E-BP1 fails to transform chicken embryo fibroblasts, suggesting a correlation between the oncogenicity of Akt and phosphorylation of S6K and 4E-BP1. The macrolide antibiotic rapamycin effectively blocks oncogenic transformation induced by either P3k or Akt but does not reduce the transforming activity of 11 other oncoproteins. Rapamycin inhibits the kinase mTOR, an important regulator of translation, and this inhibition requires binding of the antibiotic to the immunophilin FKBP12. Displacement of rapamycin from FKBP12 relieves the inhibition of mTOR and also restores P3k-induced transformation. These data are in accord with the hypothesis that transformation by P3k or Akt involves intervention in translational controls.

Diseases/Pathways annotated by Medline MESH: Cell Transformation, Neoplastic
Document information provided by NCBI PubMed

Text Mining Data

Akt → 4E-BP1: " A mutant of Akt that retains kinase activity but does not induce phosphorylation of S6K or of 4E-BP1 fails to transform chicken embryo fibroblasts, suggesting a correlation between the oncogenicity of Akt and phosphorylation of S6K and 4E-BP1 "

immunophilin FKBP12 → mTOR: " Rapamycin inhibits the kinase mTOR , an important regulator of translation, and this inhibition requires binding of the antibiotic to the immunophilin FKBP12 "

Manually curated Databases

No curated data.