| Autor: |
Roelants FM; 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. roelants@berkeley.edu., Leskoske KL; 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. kleskoske@berkeley.edu., Martinez Marshall MN; 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. nmartinezm@berkeley.edu., Locke MN; 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. mnlocke@berkeley.edu., Thorner J; 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. jthorner@berkeley.edu. |
| Abstrakt: |
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. |
