Ppm1E is an in cellulo AMP-activated protein kinase phosphatase

Voß, Martin; Paterson, James; Kelsall, Ian R.; Martín-Granados, Cristina; Hastie, C. James; Peggie, Mark; Cohen, Patricia T.W.

doi:10.1016/j.cellsig.2010.08.010

Cited by 100 publications

(73 citation statements)

References 29 publications

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“…The evidence presented here for a role of Ptc1 in regulating activation loop phosphorylation of SNF1 in yeast is in accord with a report implicating Ppm1E, and probably Ppm1F, in dephosphoryation of AMPK in mammalian cells (18). We note that Ptc1 is a less major player than Reg1-Glc7 PP1 in yeast and that other studies in mammalian cells implicated a member of the PP1 family, PP1-R6, in dephosphorylation of AMPK (19).…”

Section: Discussionsupporting

confidence: 76%

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Ptc1 Protein Phosphatase 2C Contributes to Glucose Regulation of SNF1/AMP-activated Protein Kinase (AMPK) in Saccharomyces cerevisiae

Ruiz

Carlson

2013

Journal of Biological Chemistry

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Background: SNF1/AMP-activated protein kinases (AMPKs) are central energy regulators that are inactivated by dephosphorylation of the activation loop. Results: Mutation of Ptc1 protein phosphatase 2C (PP2C) affects dephosphorylation of SNF1/AMPK in Saccharomyces cerevisiae. Conclusion: Ptc1 and Sit4 type 2A-related phosphatase contribute to glucose-regulated dephosphorylation, whereas Reg1-Glc7 PP1 plays the major role. Significance: At least three phosphatases regulate yeast SNF1/AMPK in vivo.

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Section: Discussionsupporting

confidence: 76%

“…Type 2A and 2C␣ protein phosphatases dephosphorylate the activation loop Thr in vitro (16,17); however, studies of mammalian cells implicated Ppm1E, and probably Ppm1F (18), and PP1-R6, a member of the PP1 family (19). The S. cerevisiae homolog of Ppm1E and Ppm1F is Ptc1, which is named for its identity as a PP2C family member.…”

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confidence: 99%

Ptc1 Protein Phosphatase 2C Contributes to Glucose Regulation of SNF1/AMP-activated Protein Kinase (AMPK) in Saccharomyces cerevisiae

Ruiz

Carlson

2013

Journal of Biological Chemistry

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“…We next assessed the involvement of other protein phosphatases in maintaining Snf1 Thr210 in the dephosphorylated state during growth in glucose. PP2A and PP2Cα dephosphorylate the corresponding Thr of mammalian AMPK in vitro (9,(33)(34)(35), Ppm1E and PP1-R6 have been implicated in mammalian cells (36,37), and mammalian PP2A inactivates SNF1 in vitro (6). The PP2C family in S. cerevisiae includes seven members (Ptc1 to Ptc7); Ptc1 is the most closely related to Ppm1E.…”

Section: Reg1-glc7 Contributes To Dephosphorylation Of Activated Snf1 Inmentioning

confidence: 99%

Roles of two protein phosphatases, Reg1-Glc7 and Sit4, and glycogen synthesis in regulation of SNF1 protein kinase

Ruiz

Carlson

2011

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

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The SNF1 protein kinase of Saccharomyces cerevisiae is a member of the SNF1/AMP-activated protein kinase family, which is essential for metabolic control, energy homeostasis, and stress responses in eukaryotes. SNF1 is activated in response to glucose limitation by phosphorylation of Thr210 on the activation loop of the catalytic subunit Snf1. The SNF1 β-subunit contains a glycogen-binding domain that has been implicated in glucose inhibition of Snf1 Thr210 phosphorylation. To assess the role of glycogen, we examined Snf1 phosphorylation in strains with altered glycogen metabolism. A reg1Δ mutant, lacking Reg1-Glc7 protein phosphatase 1, exhibits elevated glycogen accumulation and phosphorylation of Snf1 during growth on high levels of glucose. Unexpectedly, mutations that abolished glycogen synthesis also restored Thr210 dephosphorylation in glucose-grown reg1Δ cells, indicating that elevated glycogen synthesis contributes to activation of SNF1 and that another phosphatase acts on Snf1. We present evidence that Sit4, a type 2A-like protein phosphatase, contributes to dephosphorylation of Snf1 Thr210. Finally, evidence that the effects of glycogen are not mediated by binding to the β-subunit raises the possibility that elevated glycogen synthesis alters glucose metabolism and thereby reduces glucose signaling to the SNF1 pathway.glucose regulation | signal transduction | yeast T he SNF1/AMP-activated protein kinase (AMPK) family is conserved from yeast to mammals and is essential for metabolic control and energy homeostasis (1, 2). The Saccharomyces cerevisiae SNF1 protein kinase is required for adaptation to glucose limitation and other stresses and for growth on carbon sources that are less preferred than glucose; it is named for the sucrose-nonfermenting phenotype of the snf1 mutant (2). SNF1 regulates transcription of a large set of genes (3) and the activity of metabolic enzymes involved in carbohydrate storage and fatty acid metabolism (4-6).

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“…One strategy to induce AMPK activation is to inhibit the expression of its phosphatases [32], which were largely unknown until recently [33]. Protein phosphatase Mg 2+/ Mn 2+ -dependent (Ppm) 1e (Ppm1e) is an important AMPKα phosphatase [33].…”

Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

Fan¹,

Zhang²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. Materials: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. Results: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg^2+/ Mn²⁺-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. Conclusion: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling.

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Ppm1E is an in cellulo AMP-activated protein kinase phosphatase

Cited by 100 publications

References 29 publications

Ptc1 Protein Phosphatase 2C Contributes to Glucose Regulation of SNF1/AMP-activated Protein Kinase (AMPK) in Saccharomyces cerevisiae

Ptc1 Protein Phosphatase 2C Contributes to Glucose Regulation of SNF1/AMP-activated Protein Kinase (AMPK) in Saccharomyces cerevisiae

Roles of two protein phosphatases, Reg1-Glc7 and Sit4, and glycogen synthesis in regulation of SNF1 protein kinase

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

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