Gene interactions and pathways from curated databases and text-mining
Autophagy 2010, PMID: 20364113

Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells.

Sini, Patrizia; James, Dominic; Chresta, Christine; Guichard, Sylvie

mTOR is a major biological switch, coordinating an adequate response to changes in energy uptake (amino acids, glucose), growth signals (hormones, growth factors) and environmental stress. mTOR kinase is highly conserved through evolution from yeast to man and in both cases, controls autophagy and cellular translation in response to nutrient stress. mTOR kinase is the catalytic component of two distinct multiprotein complexes called mTORC1 and mTORC2. In addition to mTOR, mTORC1 contains Raptor, mLST8 and PRAS40. mTORC2 contains mTOR, Rictor, mSIN1 and Protor-1. mTORC1 activates p70S6K, which in turn phosphorylates the ribosomal protein S6 and 4E-BP1, both involved in protein translation. mTORC2 activates AKT directly by phosphorylating Serine 473. pAKT(S473) phosphorylates TSC2 (tuberin) and inactivates it, preventing its association with TSC1 (hamartin) and the inhibition of Rheb, an activator of mTOR. pAKT also phosphorylates PRAS40, releasing it from the mTORC1 complex, increasing its kinase activity. Finally, AKT regulates FOXO3 phosphorylation, sequestering it in the cytosol in an inactive state.

Diseases/Pathways annotated by Medline MESH: Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

p70S6K → mTORC1: " mTORC1 activates p70S6K , which in turn phosphorylates the ribosomal protein S6 and 4E-BP1, both involved in protein translation "

AKT → mTORC2: " mTORC2 activates AKT directly by phosphorylating Serine 473 "

FOXO3 → AKT: " Finally, AKT regulates FOXO3 phosphorylation, sequestering it in the cytosol in an inactive state "

Manually curated Databases

No curated data.