Protein phosphatases of Saccharomyces cerevisiae

Offley, Sarah; Schmidt, Martin C.

doi:10.1007/s00294-018-0884-y

Cited by 34 publications

(27 citation statements)

References 117 publications

(161 reference statements)

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“…Yeast PP1 phosphatase is composed of the catalytic subunit Glc7 associated with a number of alternative regulatory subunits [ 14 ]. The Glc7/Reg1 complex is the isoform of PP1 that participates in glucose repression by dephosphorylating the kinase Snf1 [ 24 – 26 ] and the transcription factor Mig1 [ 25 , 27 ].…”

Section: Resultsmentioning

confidence: 99%

“…This same allele had been isolated previously in a screen for Snf1 kinase function in the absence of the complex's gamma subunit, Snf4 [16]. Three recessive alleles produced missense mutations in the yeast protein phosphatase I complex comprised of Glc7 and Reg1 [14]. We isolated glc7-Q48K twice and reg1-P231L once.…”

Section: Isolation and Identification Of Spontaneous 2dg-resistant Mumentioning

confidence: 97%

“…Yeast PP1 phosphatase is composed of the catalytic subunit Glc7 associated with a number of alternative regulatory subunits [14]. The Glc7/Reg1 complex is the isoform of PP1 that [30] and express high levels of invertase even in the presence of glucose ( Fig 2B).…”

Section: Recessive Missense Alleles In Pp1 Phosphatase Genes Reg1 Anmentioning

confidence: 99%

“…An alternative genetic screen for 2DG-resistance using an overexpression strategy identified the 2-deoxyglucose-6-phosphatate phosphatase (2DG-6P) genes, DOG1 and DOG2 [13]. These genes encode phosphatases in the HAD-family (halo-acid dehalogenase) most closely related to the glycerol-3-phosphate phosphatases (GPP1 and GPP2) with the signature catalytic motif DxDxT [14] present at their N-termini. It has been proposed that these phosphatases confer resistance to 2DG by dephosphorylating the 2DG-6P produced when hexose kinases act on cellular 2DG; 2DG-6P is thought to be a toxic metabolite that accumulates within the cell after treatment with 2DG, however metabolomics studies of 2DG-treated cells are needed to confirm this idea.…”

Section: Introductionmentioning

confidence: 99%

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Spontaneous mutations that confer resistance to 2-deoxyglucose act through Hxk2 and Snf1 pathways to regulate gene expression and HXT endocytosis

et al. 2020

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Yeast and fast-growing human tumor cells share metabolic similarities in that both cells use fermentation of glucose for energy and both are highly sensitive to the glucose analog 2deoxyglucose. Spontaneous mutations in S. cerevisiae that conferred resistance to 2-deoxyglucose were identified by whole genome sequencing. Missense alleles of the HXK2, REG1, GLC7 and SNF1 genes were shown to confer significant resistance to 2-deoxyglucose and all had the potential to alter the activity and or target selection of the Snf1 kinase signaling pathway. All three missense alleles in HXK2 resulted in significantly reduced catalytic activity. Addition of 2DG promotes endocytosis of the glucose transporter Hxt3. All but one of the 2DG-resistant strains reduced the 2DG-mediated hexose transporter endocytosis by increasing plasma membrane occupancy of the Hxt3 protein. Increased expression of the DOG (deoxyglucose) phosphatases has been associated with resistance to 2-deoxyglucose. Expression of both the DOG1 and DOG2 mRNA was elevated after treatment with 2deoxyglucose but induction of these genes is not associated with 2DG-resistance. RNAseq analysis of the transcriptional response to 2DG showed large scale, genome-wide changes in mRNA abundance that were greatly reduced in the 2DG resistant strains. These findings suggest the common adaptive response to 2DG is to limit the magnitude of the response. Genetic studies of 2DG resistance using the dominant SNF1-G53R allele in cells that are genetically compromised in both the endocytosis and DOG pathways suggest that at least one more mechanism for conferring resistance to this glucose analog remains to be discovered.

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Section: Resultsmentioning

confidence: 99%

Section: Isolation and Identification Of Spontaneous 2dg-resistant Mumentioning

confidence: 97%

“…Yeast PP1 phosphatase is composed of the catalytic subunit Glc7 associated with a number of alternative regulatory subunits [14]. The Glc7/Reg1 complex is the isoform of PP1 that [30] and express high levels of invertase even in the presence of glucose ( Fig 2B).…”

Section: Recessive Missense Alleles In Pp1 Phosphatase Genes Reg1 Anmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Spontaneous mutations that confer resistance to 2-deoxyglucose act through Hxk2 and Snf1 pathways to regulate gene expression and HXT endocytosis

et al. 2020

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“…As a common rule, the number of protein kinases exceeds in several fold the number of phosphatases. Thus, in the model yeast Saccharomyces cerevisiae there are only 43 protein phosphatases [1], in contrast to around 120 bona fide protein kinases. Quite often, the subcellular localization, substrate specificity, or activation state of PPases is determined by their interaction with other proteins, collectively called regulatory subunits.…”

Section: Introductionmentioning

confidence: 99%

Ser/Thr protein phosphatases in fungi: structure, regulation and function

2019

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Reversible phospho-dephosphorylation of proteins is a major mechanism for the control of cellular functions. By large, Ser and Thr are the most frequently residues phosphorylated in eukar-yotes. Removal of phosphate from these amino acids is catalyzed by a large family of well-conserved enzymes, collectively called Ser/Thr protein phosphatases. The activity of these enzymes has an enormous impact on cellular functioning. In this work we pre-sent the members of this family in S. cerevisiae and other fungal species, and review the most recent findings concerning their regu-lation and the roles they play in the most diverse aspects of cell biology.

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The toxic effects of yeast Ppz1 phosphatase are counteracted by subcellular relocalization mediated by its regulatory subunit Hal3

et al. 2022

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Overexpression of Saccharomyces cerevisiae protein phosphatase Ppz1 strongly impairs cell growth. Ppz1 is negatively regulated by its subunit Hal3, and Hal3 overexpression fully counteracts the toxic effects derived from high levels of the phosphatase. We show that Ppz1 localizes at the plasma membrane, and that co‐expression of Hal3 recruits Ppz1 to internal membranes (mostly vacuolar). This effect is not observed in a catalytically impaired mutant of Ppz1. Disruption of intracellular trafficking by deletion of the ESCRT‐0 component VPS27 abolishes both Hal3‐mediated relocalization of Ppz1 and normalization of cell growth, without affecting Ppz1 protein levels. We propose that Hal3 counteracts the toxic effects caused by excess of Ppz1 not only by inhibiting its enzymatic activity but also by recruiting the phosphatase to internal structures.

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Protein phosphatases of Saccharomyces cerevisiae

Cited by 34 publications

References 117 publications

Spontaneous mutations that confer resistance to 2-deoxyglucose act through Hxk2 and Snf1 pathways to regulate gene expression and HXT endocytosis

Spontaneous mutations that confer resistance to 2-deoxyglucose act through Hxk2 and Snf1 pathways to regulate gene expression and HXT endocytosis

Ser/Thr protein phosphatases in fungi: structure, regulation and function

The toxic effects of yeast Ppz1 phosphatase are counteracted by subcellular relocalization mediated by its regulatory subunit Hal3

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