Evolutionary Conservation of the Components in the TOR Signaling Pathways

Biomolecules. 2017 Nov 1;7(4):77. doi: 10.3390/biom7040077.

Abstract

Target of rapamycin (TOR) is an evolutionarily conserved protein kinase that controls multiple cellular processes upon various intracellular and extracellular stimuli. Since its first discovery, extensive studies have been conducted both in yeast and animal species including humans. Those studies have revealed that TOR forms two structurally and physiologically distinct protein complexes; TOR complex 1 (TORC1) is ubiquitous among eukaryotes including animals, yeast, protozoa, and plants, while TOR complex 2 (TORC2) is conserved in diverse eukaryotic species other than plants. The studies have also identified two crucial regulators of mammalian TORC1 (mTORC1), Ras homolog enriched in brain (RHEB) and RAG GTPases. Of these, RAG regulates TORC1 in yeast as well and is conserved among eukaryotes with the green algae and land plants as apparent exceptions. RHEB is present in various eukaryotes but sporadically missing in multiple taxa. RHEB, in the budding yeast Saccharomyces cerevisiae, appears to be extremely divergent with concomitant loss of its function as a TORC1 regulator. In this review, we summarize the evolutionarily conserved functions of the key regulatory subunits of TORC1 and TORC2, namely RAPTOR, RICTOR, and SIN1. We also delve into the evolutionary conservation of RHEB and RAG and discuss the conserved roles of these GTPases in regulating TORC1.

Keywords: GTPase; RAG; RHEB; TORC1; TORC2; kinase; signaling; target of rapamycin (TOR).

Publication types

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

MeSH terms

  • Conserved Sequence / genetics
  • Eukaryota / genetics
  • Evolution, Molecular*
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / chemistry
  • Mechanistic Target of Rapamycin Complex 1 / genetics*
  • Mechanistic Target of Rapamycin Complex 2 / chemistry
  • Mechanistic Target of Rapamycin Complex 2 / genetics*
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Plants
  • Ras Homolog Enriched in Brain Protein / chemistry
  • Ras Homolog Enriched in Brain Protein / genetics*
  • Saccharomyces cerevisiae / genetics
  • Signal Transduction

Substances

  • Multiprotein Complexes
  • Ras Homolog Enriched in Brain Protein
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2