Thinking globally and acting locally with TOR

Curr Opin Cell Biol. 2006 Dec;18(6):589-97. doi: 10.1016/j.ceb.2006.09.005. Epub 2006 Oct 12.

Abstract

The target of rapamycin (TOR) pathway regulates ribosome biogenesis, protein synthesis, nutrient import, autophagy and cell cycle progression. After 30 years of concentrated attention, how TOR controls these processes is only now beginning to be understood. Recent advances have identified a wide array of TOR inputs, including amino acids, oxygen, ATP and growth factors, as well the regulatory proteins that facilitate their effects on TOR. Such proteins include AMPK, Rheb and the tumor suppressors LKB1, p53, and Tsc1/2. It has only recently been appreciated that TOR resides in two distinct signaling complexes with differing regulatory roles, only one of which is rapamycin-sensitive, thus opening a new avenue of inquiry into TOR function. Finally, TOR appears to regulate feeding behavior by facilitating communication between organ systems, and is thus implicated in the regulation of glucose and fat homeostasis, and possibly diabetes and obesity. TOR thus functions to coordinate growth-permitting inputs with growth-promoting outputs on both a cellular and an organismal level.

Publication types

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

MeSH terms

  • Animals
  • Appetite Regulation / physiology
  • Cell Enlargement
  • Energy Metabolism / physiology
  • Evolution, Molecular
  • Homeostasis / physiology*
  • Humans
  • Protein Serine-Threonine Kinases
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae Proteins / agonists
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction / physiology*
  • Transport Vesicles / genetics
  • Transport Vesicles / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Protein Serine-Threonine Kinases
  • target of rapamycin protein, S cerevisiae