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The TORC2‐Dependent Signaling Network in the Yeast Saccharomyces cerevisiae

Division of Biochemistry, Biophysics and Structural Biology and Division of Cell and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720‐3202, USA
Author to whom correspondence should be addressed.
Academic Editors: Kazuhiro Shiozaki and Ted Powers
Biomolecules 2017, 7(3), 66;
Received: 2 August 2017 / Revised: 25 August 2017 / Accepted: 28 August 2017 / Published: 5 September 2017
(This article belongs to the Special Issue TOR Signaling Pathway)
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. View Full-Text
Keywords: protein kinase; protein phosphorylation; regulation; metabolic control; mutants protein kinase; protein phosphorylation; regulation; metabolic control; mutants
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Roelants, F.M.; Leskoske, K.L.; Martinez Marshall, M.N.; Locke, M.N.; Thorner, J. The TORC2‐Dependent Signaling Network in the Yeast Saccharomyces cerevisiae. Biomolecules 2017, 7, 66.

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