Journal
GENES & DEVELOPMENT
Volume 32, Issue 23-24, Pages 1576-1590Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.318709.118
Keywords
signal transduction; protein kinase; regulation; yeast; mutants
Categories
Funding
- National Institutes of Health (NIH) [GM07232]
- University of California at Berkeley MacArthur and Lakhan-Pal Graduate Fellowship
- Erwin Schroedinger Fellowship from the Austrian Science Fund [J3787-B21]
- Marie Sklodowska-Curie Individual Fellowship from the European Commission [GA 750835]
- NIH S10 Equipment [OD018136]
- NIH R01 research grant [GM21841]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM021841] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD018136] Funding Source: NIH RePORTER
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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 mitogenactivated protein kinase (MAPK) of the cell wall integrity pathway. Activation of Slt2 by overexpression of a constitutively active allele of an upstream Slt2 activator (Pkcl) 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 Ypkl. 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 Ypkl 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.
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