mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer

Trends Mol Med. 2007 Jun;13(6):252-9. doi: 10.1016/j.molmed.2007.04.002. Epub 2007 Apr 23.

Abstract

Recent studies demonstrate that the mammalian target of rapamycin (mTOR) and its effector, S6 kinase 1 (S6K1), lie at the crossroads of a nutrient-hormonal signaling network that is involved in specific pathological responses, including obesity, diabetes and cancer. mTOR exists in two complexes: mTOR Complex1, which is rapamycin-sensitive and phosphorylates S6K1 and initiation factor 4E binding proteins (4E-BPs), and mTOR Complex2, which is rapamycin-insensitive and phosphorylates protein kinase B (PKB, also known as Akt). Both mTOR complexes are stimulated by mitogens, but only mTOR Complex1 is under the control of nutrient and energy inputs. Thus, to orchestrate the control of homeostatic responses, mTOR Complex1 must integrate signals from distinct cues. Here, we review recent findings concerning the regulation and pathophysiology associated with mTOR Complex1 and S6K1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus / enzymology*
  • Humans
  • Neoplasms / enzymology*
  • Obesity / enzymology*
  • Protein Kinases / metabolism*
  • Ribosomal Protein S6 Kinases / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases

Substances

  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases