Novel regulatory mechanisms of mTOR signaling

Curr Top Microbiol Immunol. 2004;279:245-57. doi: 10.1007/978-3-642-18930-2_14.


As a master regulator of cellular processes ranging from cell growth and proliferation to differentiation, the mammalian target of rapamycin (mTOR) is critically involved in a complex signaling network. mTOR appears to govern an amino acid sensing pathway that integrates with a phosphatidylinositol 3-kinase-dependent mitogenic pathway to activate the downstream effectors. Recent findings have revealed some unexpected regulatory mechanisms of mTOR signaling. A direct link between mTOR and mitogenic signals is found to be mediated by the lipid second messenger phosphatidic acid. In addition, cytoplasmic-nuclear shuttling of mTOR appears to be required for the cytoplasmic functions of this protein. A new picture of the rapamycin-sensitive signaling network is emerging, with implications in putative upstream regulators and additional downstream targets for mTOR.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinases / physiology
  • Phosphatidic Acids / physiology*
  • Protein Kinases / physiology*
  • Ribosomal Protein S6 Kinases / physiology
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases


  • Phosphatidic Acids
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Ribosomal Protein S6 Kinases
  • Mitogen-Activated Protein Kinases