hvps34, an ancient player, enters a growing game: mTOR Complex1/S6K1 signaling

Curr Opin Cell Biol. 2007 Apr;19(2):135-41. doi: 10.1016/j.ceb.2007.02.019. Epub 2007 Feb 23.

Abstract

Recent studies have shown that the nutrient input to the mTOR Complex1/S6K1 signaling pathway is mediated by class 3 PI3K or hVps34, the oldest member of the PI3K family. Moreover, studies to date would suggest that during the evolution of multicellular organisms this ancient branch of the pathway was merged with the growth-factor-hormone-controlled class 1 PI3K pathway at the level of mTOR Complex1 to control the development and growth of the organism. However, hVps34 also plays a role in the regulation of macroautophagy - the mechanism by which cells generate nutrients, such as amino acids, through the degradation of intracellular complexes, including mitochondria and ribosomes. These functions of hVps34 initially appear contradictory, since increased mTOR Complex1 activation is triggered by increased amino acid levels, while autophagy is triggered when cells are faced with amino acid deprivation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autophagy
  • Endosomes / metabolism
  • Humans
  • Models, Biological
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Kinases / metabolism*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases

Substances

  • Protein Kinases
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • ribosomal protein S6 kinase, 70kD, polypeptide 1