REG1 binds to protein phosphatase type 1 and regulates glucose repression in Saccharomyces cerevisiae.

Abstract Protein phosphatase type 1 (PP1) is encoded by the essential gene GLC7 in Saccharomyces cerevisiae. glc7-109 (K259A, R260A) has a dominant, hyperglycogen defect and a recessive, ion and drug sensitivity. Surprisingly, the hyperglycogen phenotype is partially retained in null mutants of GAC1, GIP2, and PIG1, which encode potential glycogen-targeting subunits of Glc7. The R260A substitution in GLC7 is responsible for the dominant and recessive traits of glc7-109. Another mutation at this residue, glc7-R260P, confers only salt sensitivity, indicating that the glycogen and salt traits of glc7-109 are due to defects in distinct physiological pathways. The glc7-109 mutant is sensitive to cations, aminoglycosides, and alkaline pH and exhibits increased rates of l-leucine and 3,3′-dihexyloxacarbocyanine iodide uptake, but it is resistant to molar concentrations of sorbitol or KCl, indicating that it has normal osmoregulation. KCl suppresses the ion and drug sensitivities of the glc7-109 mutant. The CsCl sensitivity of this mutant is suppressed by recessive mutations in PMA1, which encodes the essential plasma membrane H+ATPase. Together, these results indicate that Glc7 regulates ion homeostasis by controlling ion transport and/or plasma membrane potential, a new role for Glc7 in budding yeast.

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GAC1 may encode a regulatory subunit for protein phosphatase type 1 in Saccharomyces cerevisiae.

The EMBO Journal ◽

10.1002/j.1460-2075.1992.tb05031.x ◽

1992 ◽

Vol 11 (1) ◽

pp. 87-96 ◽

Cited By ~ 97

Author(s):

J.M. François ◽

S. Thompson-Jaeger ◽

J. Skroch ◽

U. Zellenka ◽

W. Spevak ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Protein Phosphatase ◽

Regulatory Subunit ◽

Protein Phosphatase Type 1 ◽

Protein Phosphatase Type

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Alanine-Scanning Mutagenesis of Protein Phosphatase Type 1 in the Yeast Saccharomyces cerevisiae

Genetics ◽

10.1093/genetics/145.3.615 ◽

1997 ◽

Vol 145 (3) ◽

pp. 615-626 ◽

Cited By ~ 12

Author(s):

Stefanie H Baker ◽

Debra L Frederick ◽

Andrew Bloecher ◽

Kelly Tatchell

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Protein Phosphatase ◽

Diverse Range ◽

Cycle Arrest ◽

Protein Phosphatase Type 1 ◽

Wide Range ◽

Protein Phosphatase Type

Protein phosphatase type 1, encoded by GLC7 in Saccharomyces cerevisiae, is an essential serine/threonine phosphatase implicated in the regulation of a diverse array of physiological functions. We constructed and examined 20 mutant alleles of GLC7 in which codons encoding clusters of charged residues were changed to alanine codons. Three of 20 mutant alleles alter residues in the active site of the phosphatase and are unable to rescue the lethality of a glc7::LEU2 disruption. The 17 alleles that support growth confer a range of mutant traits including cell cycle arrest, 2-deoxyglucose resistance, altered levels of glycogen, sensitivity to high salt, and sporulation defects. For some traits, such as 2-deoxyglucose resistance and cell cycle arrest, the mutated residues map to specific regions of the protein whereas the mutated residues in glycogen-deficient mutants and sporulation-defective mutants are more widely distributed over the protein surface. Many mutants have complex phenotypes, each displaying a diverse range of defects. The wide range of phenotypes identified from the collection of mutant alleles is consistent with the hypothesis that Glc7p-binding proteins, which are thought to regulate the specificity of Glc7p, have overlapping binding sites on the surface of Glc7p. This could account for the high level of sequence conservation found among type 1 protein phosphatases from different species.

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Genetic Interactions Between REG1/HEX2 and GLC7, the Gene Encoding the Protein Phosphatase Type 1 Catalytic Subunit in Saccharomyces cerevisiae

Genetics ◽

10.1093/genetics/143.1.119 ◽

1996 ◽

Vol 143 (1) ◽

pp. 119-127 ◽

Cited By ~ 7

Author(s):

Dongqing Huang ◽

Kristin T Chun ◽

Mark G Goebl ◽

Peter J Roach

Keyword(s):

Protein Phosphatase ◽

Glucose Repression ◽

Glycogen Synthesis ◽

Catalytic Subunit ◽

Loss Of Function ◽

Gene Encoding ◽

Glycogen Accumulation ◽

Protein Phosphatase Type 1 ◽

Protein Phosphatase Type

Abstract Mutations in GLC7, the gene encoding the type 1 protein phosphatase catalytic subunit, cause a variety of abberrant phenotypes in yeast, such as impaired glycogen synthesis and relief of glucose repression of the expression of some genes. Loss of function of the REG1/HEX2 gene, necessary for glucose repression of several genes, was found to suppress the glycogendeficient phenotype of the glc7-1 allele. Deletion of REG1 in a wild-type background led to overaccumulation of glycogen as well as slow growth and an enlarged cell size. However, loss of REG1 did not suppress other phenotypes associated with GLC7 mutations, such as inability to sporulate or, in cells bearing the glc7Y-170 allele, lack of growth at 14°. The effect of REG1 deletion on glycogen accumulation is not simply due to derepression of glucose-repressed genes, although it does require the presence of SAF1, which encodes a protein kinase essential for expression of glucose-repressed genes and for glycogen accumulation. We propose that REG1 has a role in controlling glycogen accumulation.

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Protein phosphatase type-1 and type-2 catalytic subunits both bind inhibitor-2 and monoclonal immunoglobulins.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)66805-x ◽

1986 ◽

Vol 261 (32) ◽

pp. 14924-14928 ◽

Cited By ~ 5

Author(s):

D L Brautigan ◽

P A Gruppuso ◽

M Mumby

Keyword(s):

Protein Phosphatase ◽

Catalytic Subunits ◽

Protein Phosphatase Type 1 ◽

Monoclonal Immunoglobulins ◽

Protein Phosphatase Type

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Ectopic Expression of Inhibitors of Protein Phosphatase Type 1 (PP1) Can Be Used to Analyze Roles of PP1 in Drosophila Development

Genetics ◽

10.1093/genetics/164.1.235 ◽

2003 ◽

Vol 164 (1) ◽

pp. 235-245

Author(s):

Daimark Bennett ◽

Balázs Szöőr ◽

Sascha Gross ◽

Natalia Vereshchagina ◽

Luke Alphey

Keyword(s):

Protein Phosphatase ◽

Muscle Development ◽

Ectopic Expression ◽

High Specificity ◽

Type I ◽

Protein Phosphatase Type 1 ◽

Mitotic Figures ◽

Protein Phosphatase Type

Abstract We have identified two proteins that bind with high specificity to type 1 serine/threonine protein phosphatase (PP1) and have exploited their inhibitory properties to develop an efficient and flexible strategy for conditional inactivation of PP1 in vivo. We show that modest overexpression of Drosophila homologs of I-2 and NIPP1 (I-2Dm and NIPP1Dm) reduces the level of PP1 activity and phenotypically resembles known PP1 mutants. These phenotypes, which include lethality, abnormal mitotic figures, and defects in muscle development, are suppressed by coexpression of PP1, indicating that the effect is due specifically to loss of PP1 activity. Reactivation of I-2Dm:PP1c complexes suggests that inhibition of PP1 activity in vivo does not result in a compensating increase in synthesis of active PP1. PP1 mutants enhance the wing overgrowth phenotype caused by ectopic expression of the type II TGFβ superfamily signaling receptor Punt. Using I-2Dm, which has a less severe effect than NIPP1Dm, we show that lowering the level of PP1 activity specifically in cells overexpressing Punt is sufficient for wing overgrowth and that the interaction between PP1 and Punt requires the type I receptor Thick-veins (Tkv) but is not strongly sensitive to the level of the ligand, Decapentaplegic (Dpp), nor to that of the other type I receptors. This is consistent with a role for PP1 in antagonizing Punt by preventing phosphorylation of Tkv. These studies demonstrate that inhibitors of PP1 can be used in a tissue- and developmental-specific manner to examine the developmental roles of PP1.

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Differential expression of protein phosphatase type 1 isotypes and nucleolin during cell cycle arrest

Cell Biochemistry and Function ◽

10.1002/cbf.1300 ◽

2007 ◽

Vol 25 (4) ◽

pp. 369-375 ◽

Cited By ~ 5

Author(s):

Hiroyuki Morimoto ◽

Akiko Ozaki ◽

Hirohiko Okamura ◽

Kaya Yoshida ◽

Bruna Rabelo Amorim ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Differential Expression ◽

Protein Phosphatase ◽

Cycle Arrest ◽

Protein Phosphatase Type 1 ◽

Protein Phosphatase Type

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The GLC7 type 1 protein phosphatase is required for glucose repression in Saccharomyces cerevisiae.

Molecular and Cellular Biology ◽

10.1128/mcb.14.10.6789 ◽

1994 ◽

Vol 14 (10) ◽

pp. 6789-6796 ◽

Cited By ~ 60

Author(s):

J Tu ◽

M Carlson

Keyword(s):

Saccharomyces Cerevisiae ◽

Protein Kinase ◽

Genetic Analysis ◽

Protein Phosphatase ◽

Glucose Repression ◽

Regulatory Mechanisms ◽

Genetic Studies ◽

Glycogen Accumulation ◽

Regulatory Response

We cloned the GLC7/DIS2S1 gene by complementation of the cid1-226 mutation, which relieves glucose repression in Saccharomyces cerevisiae. GLC7 encodes the catalytic subunit of type 1 protein phosphatase (PP1). Genetic analysis and sequencing showed that cid1-226 is an allele of GLC7, now designated glc7-T152K, which alters threonine 152 to lysine. We also show that the glc7-1 and glc7-T152K alleles cause distinct phenotypes: glc7-1 causes a severe defect in glycogen accumulation but does not relieve glucose repression, whereas glc7-T152K does not prevent glycogen accumulation. These findings are discussed in light of evidence that interaction with different regulatory or targeting subunits directs the participation of PP1 in diverse cellular regulatory mechanisms. Finally, genetic studies suggest that PP1 functions antagonistically to the SNF1 protein kinase in the regulatory response to glucose.

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