Phosphorylation by the stress-activated MAPK Slt2 down-regulates the yeast TOR complex 2

Kristin L. Leskoske, Françoise M. Roelants, Anita Emmerstorfer-Augustin, Christoph M. Augustin, Edward P. Si, Jennifer M. Hill, Jeremy Thorner

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Saccharomyces cerevisiae target of rapamycin (TOR) complex 2 (TORC2) is an essential regulator of plasma membrane lipid and protein homeostasis. How TORC2 activity is modulated in response to changes in the status of the cell envelope is unclear. Here we document that TORC2 subunit Avo2 is a direct target of Slt2, the mitogen-activated protein kinase (MAPK) of the cell wall integrity pathway. Activation of Slt2 by overexpression of a constitutively active allele of an upstream Slt2 activator (Pkc1) or by auxin-induced degradation of a negative Slt2 regulator (Sln1) caused hyperphosphorylation of Avo2 at its MAPK phosphoacceptor sites in a Slt2-dependent manner and diminished TORC2-mediated phosphorylation of its major downstream effector, protein kinase Ypk1. Deletion of Avo2 or expression of a phosphomimetic Avo2 allele rendered cells sensitive to two stresses (myriocin treatment and elevated exogenous acetic acid) that the cell requires Ypk1 activation by TORC2 to survive. Thus, Avo2 is necessary for optimal TORC2 activity, and Slt2-mediated phosphorylation of Avo2 down-regulates TORC2 signaling. Compared with wild-type Avo2, phosphomimetic Avo2 shows significant displacement from the plasma membrane, suggesting that Slt2 inhibits TORC2 by promoting Avo2 dissociation. Our findings are the first demonstration that TORC2 function is regulated by MAPK-mediated phosphorylation.

Original languageEnglish
Pages (from-to)1576-1590
Number of pages15
JournalGenes and Development
Volume32
Issue number23-24
DOIs
Publication statusPublished - 1 Dec 2018

Keywords

  • Mutants
  • Protein kinase
  • Regulation
  • Signal transduction
  • Yeast

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Leskoske, K. L., Roelants, F. M., Emmerstorfer-Augustin, A., Augustin, C. M., Si, E. P., Hill, J. M., & Thorner, J. (2018). Phosphorylation by the stress-activated MAPK Slt2 down-regulates the yeast TOR complex 2. Genes and Development, 32(23-24), 1576-1590. https://doi.org/10.1101/gad.318709.118