mTOR substrate phosphorylation in growth control

Cell. 2022 May 26;185(11):1814-1836. doi: 10.1016/j.cell.2022.04.013. Epub 2022 May 16.

Abstract

The target of rapamycin (TOR), discovered 30 years ago, is a highly conserved serine/threonine protein kinase that plays a central role in regulating cell growth and metabolism. It is activated by nutrients, growth factors, and cellular energy. TOR forms two structurally and functionally distinct complexes, TORC1 and TORC2. TOR signaling activates cell growth, defined as an increase in biomass, by stimulating anabolic metabolism while inhibiting catabolic processes. With emphasis on mammalian TOR (mTOR), we comprehensively reviewed the literature and identified all reported direct substrates. In the context of recent structural information, we discuss how mTORC1 and mTORC2, despite having a common catalytic subunit, phosphorylate distinct substrates. We conclude that the two complexes recruit different substrates to phosphorylate a common, minimal motif.

Publication types

  • Review

MeSH terms

  • Animals
  • Mammals / metabolism
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • Multiprotein Complexes* / metabolism
  • Phosphorylation
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • Multiprotein Complexes
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • TOR Serine-Threonine Kinases
  • Sirolimus