The TORC2-Dependent Signaling Network in the Yeast Saccharomyces cerevisiae

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2017-09, Vol.7 (3), p.66
• Main Authors: Roelants, Françoise M, Leskoske, Kristin L, Martinez Marshall, Maria Nieves, Locke, Melissa N, Thorner, Jeremy
• Format: Article
• Language: English
• Subjects: Baking yeast; Cell Membrane - metabolism; Cell survival; Cell Wall - metabolism; Cell walls; Diglycerides; Fungi; Gene Expression Regulation, Fungal; Gene Regulatory Networks; Glycogen Synthase Kinase 3 - chemistry; Glycogen Synthase Kinase 3 - metabolism; Guanosine triphosphate; Homeostasis; Kinases; Lipids; Mechanistic Target of Rapamycin Complex 2 - chemistry; Mechanistic Target of Rapamycin Complex 2 - metabolism; Membrane proteins; metabolic control; mutants; Phosphatidylserine; Phosphorylation; Protein Binding; Protein kinase; Protein kinase C; Protein Kinase C - metabolism; Protein Kinases - metabolism; protein phosphorylation; Proteins; regulation; Review; Saccharomyces cerevisiae; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction; Sphingolipids; Sterols; Substrates; Yeast
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom7030066

To grow, eukaryotic cells must expand by inserting glycerolipids, sphingolipids, sterols, and proteins into their plasma membrane, and maintain the proper levels and bilayer distribution. A fungal cell must coordinate growth with enlargement of its cell wall. In Saccharomyces cerevisiae, a plasma membrane-localized protein kinase complex, Target of Rapamicin (TOR) complex-2 (TORC2) (mammalian ortholog is mTORC2), serves as a sensor and masterregulator of these plasma membrane- and cell wall-associated events by directly phosphorylating and thereby stimulating the activity of two types of effector protein kinases: Ypk1 (mammalian ortholog is SGK1), along with a paralog (Ypk2); and, Pkc1 (mammalian ortholog is PKN2/PRK2). Ypk1 is a central regulator of pathways and processes required for plasma membrane lipid and protein homeostasis, and requires phosphorylation on its T-loop by eisosome-associated protein kinase Pkh1 (mammalian ortholog is PDK1) and a paralog (Pkh2). For cell survival under various stresses, Ypk1 function requires TORC2-mediated phosphorylation at multiple sites near its C terminus. Pkc1 controls diverse processes, especially cell wall synthesis and integrity. Pkc1 is also regulated by Pkh1- and TORC2-dependent phosphorylation, but, in addition, by interaction with Rho1-GTP and lipids phosphatidylserine (PtdSer) and diacylglycerol (DAG). We also describe here what is currently known about the downstream substrates modulated by Ypk1-mediated and Pkc1-mediated phosphorylation.