Upstream and downstream of mTOR

Genes Dev. 2004 Aug 15;18(16):1926-45. doi: 10.1101/gad.1212704.


The evolutionarily conserved checkpoint protein kinase, TOR (target of rapamycin), has emerged as a major effector of cell growth and proliferation via the regulation of protein synthesis. Work in the last decade clearly demonstrates that TOR controls protein synthesis through a stunning number of downstream targets. Some of the targets are phosphorylated directly by TOR, but many are phosphorylated indirectly. In this review, we summarize some recent developments in this fast-evolving field. We describe both the upstream components of the signaling pathway(s) that activates mammalian TOR (mTOR) and the downstream targets that affect protein synthesis. We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity.

Publication types

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

MeSH terms

  • Animals
  • Cell Division / physiology
  • Energy Metabolism
  • Growth Substances / physiology
  • Neoplasms / physiopathology
  • Peptide Initiation Factors / physiology
  • Phosphorylation
  • Protein Biosynthesis / physiology
  • Protein Kinases / genetics
  • Protein Kinases / physiology*
  • Ribosomal Protein S6 Kinases / physiology
  • TOR Serine-Threonine Kinases
  • Transcription, Genetic / physiology


  • Growth Substances
  • Peptide Initiation Factors
  • Protein Kinases
  • Ribosomal Protein S6 Kinases
  • TOR Serine-Threonine Kinases