Protein phosphatase 2Cα expression in normal human tissues: an immunohistochemical study

Lifschitz-Mercer, Beatriz; Sheinin, Yuri; Ben-Meir, Daniella; Bramante-Schreiber, Letizia; Leider-Trejo, Leonor; Karby, Shulamit; Smorodinsky, Nechama I.; Lavi, Sara

doi:10.1007/s004180100291

Cited by 25 publications

(8 citation statements)

References 19 publications

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“…In the present study we also provide evidence that PPM1A and PPM1B redundantly dephosphorylate the α-subunit of AMPK. Although these isoforms are closely related (75 % identity), they were shown to be distinctly localized in cells [15,19,41], raising the possibility that they might act on AMPK heterotrimeric complexes at different subcellular locations within cells. Recently, Voss et al [33] reported that PPM1E is a protein phosphatase that acts on AMPK.…”

Section: Discussionmentioning

confidence: 99%

N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells

Chida

Ando

Matsuki

et al. 2013

Biochemical Journal

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PPM [metal-dependent protein phosphatase, formerly called PP2C (protein phosphatase 2C)] family members play essential roles in regulating a variety of signalling pathways. While searching for protein phosphatase(s) that act on AMPK (AMP-activated protein kinase), we found that PPM1A and PPM1B are N-myristoylated and that this modification is essential for their ability to dephosphorylate the α subunit of AMPK (AMPKα) in cells. N-Myristoylation was also required for two other functions of PPM1A and PPM1B in cells. Although a non-myristoylated mutation (G2A) of PPM1A and PPM1B prevented membrane association, this relocalization did not likely cause the decreased activity towards AMPKα. In in vitro experiments, the G2A mutants exhibited reduced activities towards AMPKα, but much higher specific activity against an artificial substrate, PNPP (p-nitrophenyl phosphate), compared with the wild-type counterparts. Taken together, the results of the present study suggest that N-myristoylation of PPM1A and PPM1B plays a key role in recognition of their physiological substrates in cells.

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Section: Discussionmentioning

confidence: 99%

N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells

Chida

Ando

Matsuki

et al. 2013

Biochemical Journal

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“…PP2Cα was expressed mainly in different epithelial cell types in organs and tissues including the skin, lungs, kidney, breast, digestive tract, endocrine glands, testis, prostate, ovary, uterus, brain, lymph nodes and bone marrow. Human endothelial cells, smooth muscle cells and extracellular matrix contained no or very little PP2Cα 77 . In contrast with the other Ser/Thr protein phosphatases, how the activity, localization and substrate specificity of PP2C are governed is not clear 76 .…”

Section: Regulation Of Ampk In Endothelial Cellsmentioning

confidence: 99%

Amp‐activated Protein Kinase Activation as a Strategy for Protecting Vascular Endothelial Function

Zou

2007

Clin Exp Pharma Physio

109

100

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SUMMARY1. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase involved in the regulation of cellular and organismal metabolism. AMPK has a heterotrimeric structure, consisting of a catalytic a-subunit and regulatory b-and g-subunits, each of which has two or more isoforms that are differentially expressed in various tissues and that arise from distinct genes. The AMPK system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. In addition, AMPK is activated by physiological stimuli and oxidants.2. The importance of AMPK in cardiovascular functions is best demonstrated by recent studies showing that widely used drugs, including statins, metformin and rosiglitazone, execute cardiovascular protective effects at least partly through the activation of AMPK. As a consequence, AMPK has been proposed as a candidate target for therapeutic intervention in the treatment of both Type 2 diabetes and metabolic syndrome owing to its central role in the regulation of energy balance; it may also have a role in weight control.3. In the present brief review, we summarize the recent progress of AMPK signalling and regulation focusing on vascular endothelial cells. We further hypothesize that AMPK is a dual sensor for energy and redox status within a cell and AMPK may be a therapeutic target for protecting vascular endothelial function.Key words: AMP-activated kinase, atherosclerosis, diabetes mellitus, endothelium, energy metabolism, hypertension, nitric oxide, oxidative stress, peroxynitrite, superoxide anions. OVERALL REVIEW OF AMP-ACTIVATED KINASEThe AMP-activated protein kinase (AMPK) is a serine/threonine kinase and a member of the Snf1/AMPK protein kinase family that is found in all eukaryotes. 1,2 AMPK has been proposed to act as a cellular energy sensor, which switches on catabolic pathways that produce ATP and switches off anabolic pathways that consume ATP. AMPK is a heterotrimer, containing a-, b-and g-subunits, each of which has at least two isoforms. The a-subunit contains the catalytic site; however, all subunits are necessary for full activity. Increases in the ratio of AMP to ATP activate AMPK by a number of mechanisms, including direct allosteric activation and covalent modification due to activation by an AMP-dependent AMPK kinase (AMPKK), which phosphorylates the a-subunit on Thr 172 . Until recently, it was believed that this occurred as a result of activation of AMPKK by an increase in the AMP/ATP ratio. However, recent studies from Woods et al. 3 and Carlson et al. 4 failed to demonstrate such an increase in AMPKK activity in response to various AMPK activators. Rather, their results indicate that AMP binds to AMPK and that this makes it more susceptible to phosphorylation by AMPKK. Interestingly, the first AMPKK that has been identified is LKB1, a tumour suppressor that is mutated in humans with Peutz-Jegher syndrome, 5 a disorder associated with an increased risk of developing carcinomas of the colon, stomach and pancreas. A second AMPKK has been identif...

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“…As an example of the predictive value of this assay, analysis in the Ppm1a-CreER T2 line is described here, in which CreER T2 expression is driven by the promoter of the ubiquitous "protein phosphatase 1A, magnesiumdependent, alpha isoform" gene (Lifschitz-Mercer et al, 2001). Also described is the Vil1-CreER T2 mouse line, in which the recombinase is targeted to the epithelial cells of the intestinal crypts (Meseguer and Catterall, 1987;Pinto et al, 1999;Robine et al, 1997).…”

Section: Specificity and Efficiency Of Cre Expressionmentioning

confidence: 99%

Characterization and Validation of Cre‐Driver Mouse Lines

et al. 2011

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Conditional gene manipulations in mice are increasingly popular strategies in biomedical research. These approaches rely on the production of conditional genetically engineered mutant mouse (GEMM) lines with mutations in protein-encoding genes. These conditional GEMMs are then bred with one or several transgenic mouse lines expressing a site-specific recombinase, most often the Cre recombinase, in a tissue-specific manner. Conditional GEMMs can only be exploited if Cre transgenic mouse lines are available to generate somatic mutations, and thus the number of Cre transgenic lines has significantly increased over the last 15 years. Once produced, these transgenic lines must be validated for reliable, efficient, and specific Cre expression and Cre-mediated recombination. In this overview, the minimum level of information that is ideally required to validate a Cre-driver transgenic line is first discussed. The vagaries associated with validation procedures are considered next, and some solutions are proposed to assess the expression and activity of constitutive or inducible Cre recombinase before undertaking extensive breeding experiments and exhaustive phenotyping. Curr. Protoc. Mouse Biol. 1:1-15. © 2011 by John Wiley & Sons, Inc.

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Protein phosphatase 2Cα expression in normal human tissues: an immunohistochemical study

Cited by 25 publications

References 19 publications

N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells

N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells

Amp‐activated Protein Kinase Activation as a Strategy for Protecting Vascular Endothelial Function

Characterization and Validation of Cre‐Driver Mouse Lines

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