Phosphoproteomic responses of TORC1 target kinases reveal discrete and convergent mechanisms that orchestrate the quiescence program in yeast

Cell Rep. 2021 Dec 28;37(13):110149. doi: 10.1016/j.celrep.2021.110149.

Abstract

The eukaryotic TORC1 kinase assimilates diverse environmental cues, including growth factors and nutrients, to control growth by tuning anabolic and catabolic processes. In yeast, TORC1 stimulates protein synthesis in response to abundant nutrients primarily through its proximal effector kinase Sch9. Conversely, TORC1 inhibition following nutrient limitation unlocks various distally controlled kinases (e.g., Atg1, Gcn2, Npr1, Rim15, Slt2/Mpk1, and Yak1), which cooperate through poorly defined circuits to orchestrate the quiescence program. To better define the signaling landscape of the latter kinases, we use in vivo quantitative phosphoproteomics. Through pinpointing known and uncharted Npr1, Rim15, Slt2/Mpk1, and Yak1 effectors, our study examines the architecture of the distally controlled TORC1 kinase network. Accordingly, this is built on a combination of discrete, convergent, and multilayered feedback regulatory mechanisms, which likely ensure homeostatic control of and/or robust responses by TORC1 and its effector kinases under fluctuating nutritional conditions.

Keywords: Atg9; Gis1; Npr1; Rim15; Slt2/Mpk1; TORC1; Yak1; autophagy; phosphoproteomics; quiescence program; target of rapamycin complex 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Fungal / drug effects*
  • Mechanistic Target of Rapamycin Complex 1 / pharmacology*
  • Phosphoproteins / metabolism*
  • Protein Kinases / chemistry*
  • Proteome / analysis
  • Proteome / metabolism*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Phosphoproteins
  • Proteome
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • Mechanistic Target of Rapamycin Complex 1