Phosphorylation of lipid metabolic enzymes by yeast protein kinase C requires phosphatidylserine and diacylglycerol

Dey, Prabuddha; Su, Wen‐Min; Han, Gil‐Soo; Carman, George M.

doi:10.1194/jlr.m075036

Cited by 26 publications

(27 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quite recently, this issue was revisited for protein substrates thought to be bona fide in vivo targets of Pkc1. For peptides containing sites from Pah1 (PtdOH phosphatase), Nem1 (catalytic subunit of a protein phosphatase that dephosphorylates Pah1), and Spo7 (regulatory subunit of the protein phosphatase that dephosphorylates Pah1), the efficiency of their phosphorylation was not enhanced by the presence of lipids [ 233 ]. However, when the same full-length proteins (Pah1, Nem1, and Spo7) were used as substrates, PtdSer and DAG were required for their phosphorylation, with PtdSer having a greater effect than DAG [ 233 ].…”

Section: Structure Function and Regulation Of Pkc1mentioning

confidence: 99%

“…For peptides containing sites from Pah1 (PtdOH phosphatase), Nem1 (catalytic subunit of a protein phosphatase that dephosphorylates Pah1), and Spo7 (regulatory subunit of the protein phosphatase that dephosphorylates Pah1), the efficiency of their phosphorylation was not enhanced by the presence of lipids [ 233 ]. However, when the same full-length proteins (Pah1, Nem1, and Spo7) were used as substrates, PtdSer and DAG were required for their phosphorylation, with PtdSer having a greater effect than DAG [ 233 ]. Moreover, in an in vitro liposome binding assay, the presence of PtdSer enhanced Pkc1 retention in a dose-dependent manner and, in cho1∆/pss1∆ cells (which lack PtdSer synthase), the degradation of Pah1, which is thought to be a Pkc1-dependent process, was attenuated, consistent with a role for PtdSer in regulating Pkc1 function in vivo [ 233 ].…”

Section: Structure Function and Regulation Of Pkc1mentioning

confidence: 99%

“…However, when the same full-length proteins (Pah1, Nem1, and Spo7) were used as substrates, PtdSer and DAG were required for their phosphorylation, with PtdSer having a greater effect than DAG [ 233 ]. Moreover, in an in vitro liposome binding assay, the presence of PtdSer enhanced Pkc1 retention in a dose-dependent manner and, in cho1∆/pss1∆ cells (which lack PtdSer synthase), the degradation of Pah1, which is thought to be a Pkc1-dependent process, was attenuated, consistent with a role for PtdSer in regulating Pkc1 function in vivo [ 233 ].…”

Section: Structure Function and Regulation Of Pkc1mentioning

confidence: 99%

“…Indeed, the subcellular location/membrane binding [ 270 ], rate of degradation [ 271 ], and PtdOH phosphatase activity of Pah1 [ 272 ] are regulated by phosphorylation and dephosphorylation. In this regard, it has been reported, over time, that Pah1 is a target for phosphorylation by Cdk1 (Cdc28-Clb), by PKA (although, which yeast isoform, Tpk1, Tpk2, and Tpk3, was not addressed), by Cdk5 (Pho85-Pho80), by casein kinase II (Cka1-Cka2-Ckb1-Ckb2 heterotetramer in yeast) [ 273 ], and also by Pkc1 [ 233 ]. Dephosphorylation of Pah1 stimulates its catalytic activity and facilitates its association with membranes, wherein its substrate resides; dephosphorylation of Pah1 is mediated by an ER-associated heterodimeric phosphoprotein phosphatase Nem1-Spo7.…”

Section: Substrates Of Pkc1mentioning

confidence: 99%

See 3 more Smart Citations

The TORC2‐Dependent Signaling Network in the Yeast Saccharomyces cerevisiae

et al. 2017

View full text Add to dashboard Cite

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 master regulator 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.

show abstract

Section: Structure Function and Regulation Of Pkc1mentioning

confidence: 99%

Section: Structure Function and Regulation Of Pkc1mentioning

confidence: 99%

Section: Structure Function and Regulation Of Pkc1mentioning

confidence: 99%

Section: Substrates Of Pkc1mentioning

confidence: 99%

See 2 more Smart Citations

The TORC2‐Dependent Signaling Network in the Yeast Saccharomyces cerevisiae

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The cho1⌬ mutant lacks the ability to synthesize PS (21,22) and thus requires the supplementation of choline or ethanolamine to synthesize PC or PE by the Kennedy pathway (1,2). Studies with cells lacking Cho1 have revealed that PS is required for protein kinase C function (23,24), tryptophan transport (25), vacuole function and morphogenesis (26), and direction of endocytic proteins to the plasma membrane (27).…”

mentioning

confidence: 99%

Yeast PAH1-encoded phosphatidate phosphatase controls the expression of CHO1-encoded phosphatidylserine synthase for membrane phospholipid synthesis

Han

Carman

2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The -encoded phosphatidate phosphatase (PAP), which catalyzes the committed step for the synthesis of triacylglycerol in, exerts a negative regulatory effect on the level of phosphatidate used for the synthesis of membrane phospholipids. This raises the question whether PAP thereby affects the expression and activity of enzymes involved in phospholipid synthesis. Here, we examined the PAP-mediated regulation of-encoded phosphatidylserine synthase (PSS), which catalyzes the committed step for the synthesis of major phospholipids via the CDP-diacylglycerol pathway. The lack of PAP in the Δ mutant highly elevated PSS activity, exhibiting a growth-dependent up-regulation from the exponential to the stationary phase of growth. Immunoblot analysis showed that the elevation of PSS activity results from an increase in the level of the enzyme encoded by Truncation analysis and site-directed mutagenesis of the promoter indicated that Cho1 expression in theΔ mutant is induced through the inositol-sensitive upstream activation sequence (UAS), a -acting element for the phosphatidate-controlled Henry (Ino2-Ino4/Opi1) regulatory circuit. The abrogation of Cho1 induction and PSS activity by a UAS mutation suppressed Δ effects on lipid synthesis, nuclear/endoplasmic reticulum membrane morphology, and lipid droplet formation, but not on growth at elevated temperature. Loss of the-encoded diacylglycerol kinase, which converts diacylglycerol to phosphatidate, partially suppressed the Δ-mediated induction of Cho1 and PSS activity. Collectively, these data showed that PAP activity controls the expression of PSS for membrane phospholipid synthesis.

show abstract