Glc7–Reg1 Phosphatase Signals to Yck1,2 Casein Kinase 1 to Regulate Transport Activity and Glucose-Induced Inactivation of Saccharomyces Maltose Permease

Gadura, Nidhi; Robinson, Lucy C.; Michels, Corinne A.

doi:10.1534/genetics.105.051698

Cited by 42 publications

(38 citation statements)

References 52 publications

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“…However, it would not explain the impaired rubidium transport and the observed incapacity to grow in low-K ϩ medium. However, Yck kinases are known to modulate the activity and/or turnover of several membrane transporters, such as the maltose permease (15) and the monocarboxylate transporter Jen1 (15). It is tempting to speculate that the Trk1 potassium trans-porter could also be affected in this mutant, and this hypothesis is supported by our analysis of the amount of Trk1 present in plasma membrane-enriched fractions (see Fig.…”

Section: Discussionsupporting

confidence: 57%

A Genomewide Screen for Tolerance to Cationic Drugs Reveals Genes Important for Potassium Homeostasis in Saccharomyces cerevisiae

et al. 2011

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Potassium homeostasis is crucial for living cells. In the yeast Saccharomyces cerevisiae, the uptake of potassium is driven by the electrochemical gradient generated by the Pma1 H ؉ -ATPase, and this process represents a major consumer of the gradient. We considered that any mutation resulting in an alteration of the electrochemical gradient could give rise to anomalous sensitivity to any cationic drug independently of its toxicity mechanism. Here, we describe a genomewide screen for mutants that present altered tolerance to hygromycin B, spermine, and tetramethylammonium. Two hundred twenty-six mutant strains displayed altered tolerance to all three drugs (202 hypersensitive and 24 hypertolerant), and more than 50% presented a strong or moderate growth defect at a limiting potassium concentration (1 mM). Functional groups such as protein kinases and phosphatases, intracellular trafficking, transcription, or cell cycle and DNA processing were enriched. Essentially, our screen has identified a substantial number of genes that were not previously described to play a direct or indirect role in potassium homeostasis. A subset of 27 representative mutants were selected and subjected to diverse biochemical tests that, in some cases, allowed us to postulate the basis for the observed phenotypes.

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Section: Discussionsupporting

confidence: 57%

A Genomewide Screen for Tolerance to Cationic Drugs Reveals Genes Important for Potassium Homeostasis in Saccharomyces cerevisiae

et al. 2011

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“…The subsequent destruction of Mth1 and Std1 inactivates the Rgt1 transcriptional repressor, resulting in derepression of HXT genes encoding hexose transporters (7,9). In response to glucose, Yck1/2 also mediates inactivation and degradation of transporters of alternative carbon sources, such as maltose (Mal61) (10) and lactate/pyruvate/acetate (Jen1) (11). Achieving this glucose-induced switching of transporters seems to be the main purpose of the SRR pathway (12).…”

mentioning

confidence: 99%

SUMOylation regulates the SNF1 protein kinase

Simpson-Lavy

Johnston

2013

Proc. Natl. Acad. Sci. U.S.A.

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The AMP-activated protein kinase (AMPK) is a major stress sensor of mammalian cells. AMPK's homolog in the yeast Saccharomyces cerevisiae, the SNF1 protein kinase, is a central regulator of carbon metabolism that inhibits the Snf3/Rgt2-Rgt1 glucose sensing pathway and activates genes involved in respiration. We present evidence that glucose induces modification of the Snf1 catalytic subunt of SNF1 with the small ubiquitin-like modifier protein SUMO, catalyzed by the SUMO (E3) ligase Mms21. Our results suggest that SUMOylation of Snf1 inhibits its function in two ways: by interaction of SUMO attached to lysine 549 with a SUMO-interacting sequence motif located near the active site of Snf1, and by targeting Snf1 for destruction via the Slx5-Slx8 (SUMO-directed) ubiquitin ligase. These findings reveal another way SNF1 function is regulated in response to carbon source.protein kinase regulation | protein modification | signal transduction G lucose is the preferred carbon source of most cells, including Saccharomyces cerevisiae, which ferments it to ethanol and CO 2 , producing only two ATPs, even when oxygen is available to drive production of much more ATP. This preference for fermentation (which cancer cells share), is known as the Crabtree or Warburg effect (1, 2). Because of the energetic inefficiency of fermentation, yeast cells must be adroit in sensing glucose. S. cerevisiae has three well-known glucose sensing pathways: (i) the Gpa1/2-Ras2-PKA pathway that regulates stress response (through Msn2/4) and other things; (ii) the SNF1 pathway, which regulates respiratory metabolism and other processes; and (iii) the Snf3/Rgt2-Rgt1 (SRR) pathway that regulates expression of genes encoding hexose transporters (3).The SRR (sensor/receptor-repressor) pathway begins at the cell surface with high-affinity (Snf3) (4) and low-affinity (Rgt2) glucose sensors (5) that are coupled to the casein kinases Yck1 and Yck2, which catalyze phosphorylation of the corepressor proteins Mth1 and Std1 (6), leading to their ubiquitinylation by SCF Grr1 (7,8). The subsequent destruction of Mth1 and Std1 inactivates the Rgt1 transcriptional repressor, resulting in derepression of HXT genes encoding hexose transporters (7, 9). In response to glucose, Yck1/2 also mediates inactivation and degradation of transporters of alternative carbon sources, such as maltose (Mal61) (10) and lactate/pyruvate/acetate (Jen1) (11). Achieving this glucose-induced switching of transporters seems to be the main purpose of the SRR pathway (12).The SNF1 protein kinase-the ortholog of the AMP-activated protein kinase (AMPK), a major stress-activated protein kinase in mammalian cells (13,14)-is a central regulator of carbon metabolism (15,16). This kinase is an activator of Adr1 and Cat8, which activate expression of genes involved in the diauxic shift, ethanol, and lactate uptake and catabolism, gluconeogenesis, and respiration (17-21), and is an inhibitor of the Mig1 repressor of glucose-repressed genes (22). SNF1 is a heterotrimer of the Snf1 catalytic subunit,...

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“…Binding of Reg1p to Glc7p is enhanced in the presence of glucose and is required for glucose repression (Gadura et al, 2006). Effective alleviation of glucose repression could increase maltose metabolism (Lin et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Effects of GLC7 and REG1 deletion on maltose metabolism and leavening ability of baker’s yeast in lean dough

Lin

Zhang

Bai

et al. 2015

Journal of Biotechnology

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Glc7–Reg1 Phosphatase Signals to Yck1,2 Casein Kinase 1 to Regulate Transport Activity and Glucose-Induced Inactivation of Saccharomyces Maltose Permease

Cited by 42 publications

References 52 publications

A Genomewide Screen for Tolerance to Cationic Drugs Reveals Genes Important for Potassium Homeostasis in Saccharomyces cerevisiae

A Genomewide Screen for Tolerance to Cationic Drugs Reveals Genes Important for Potassium Homeostasis in Saccharomyces cerevisiae

SUMOylation regulates the SNF1 protein kinase

Effects of GLC7 and REG1 deletion on maltose metabolism and leavening ability of baker’s yeast in lean dough

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