Disease relevance of PPM2C

• After mutation of 9 ciliate Q codons (TAA) to CAA PtPP2C was expressed as an active protein in Escherichia coli [1].
• The data imply that deficient activity of the PDH complex may be associated with spinocerebellar degenerations, and that the clinical phenotypes of the inherited ataxias can be associated with several genotypes [2].
• The effects of diabetes on myocardial metabolism are complex in that they are tied to the systemic metabolic abnormalities of the disease (hyperglycemia and elevated levels of free fatty acid and ketone bodies), and changes in cardiomyocyte phenotype (e.g., down-regulation of glucose transporters and PDH activity) [3].
• During the onset of exercise in hypoxia, the increased lactate accumulation is associated with a delayed activation of pyruvate dehydrogenase (PDH; Parolin ML, Spreit LL, Hultman E, Hollidge-Horvat MG, Jones NL, and Heigenhauser GJF. Am J Physiol Endocrinol Metab 278: E522-E534, 2000) [4].
• We used an image analysis facility built around a PDP 11/105 computer to measure the volume of edema as outlined by Evans blue staining [5].

Psychiatry related information on PPM2C

• PDP1 protein was not responsive to food deprivation in all fiber types [6].
• Recent interest in PDP (parallel distributed processing) models is due in part to the widely held belief that they challenge many of the assumptions of classical cognitive science [7].

High impact information on PPM2C

• A genomic clone encompassing the entire gene for the human pyruvate dehydrogenase beta subunit (PDH beta) has been isolated by screening a leukocyte genomic library with a nick-translated human foreskin fibroblast PDH beta cDNA probe [8].
• The PDH beta structural gene is composed of 10 exons and 9 introns [8].
• Primer-extension analysis indicated that the PDH beta gene transcription start site is an adenine residue located 132 bases upstream from the initiation codon in exon 1 [8].
• The 5' flanking region of the PDH beta gene contains a "CAAT" consensus promoter sequence but no "TATA" sequence [8].
• The amino acid sequences of phosphorylation sites determined in PDH alpha of bovine and porcine enzymes were also conserved in the human PDH alpha [9].

Chemical compound and disease context of PPM2C

• To study the incidence of abnormalities of the pyruvate (PDH) or ketoglutarate (KGDH) dehydrogenase complexes in patients with spinocerebellar degenerations, we measured the activities of PDH and KGDH in platelet-enriched preparations from the blood of 14 patients [2].
• Effects of PDH activation by dichloroacetate in human skeletal muscle during exercise in hypoxia [4].
• Two transplantable solid tumors (CBP and PDP) and two continuous cultured cell lines (CBP-TC and PDP-TC) were established from nitrosamine-induced pancreatic ductal adenocarcinomas in inbred Syrian hamsters [10].
• In a study including a total of 175 children, ranging in age from 3 months to 3 years and suffering from otitis media, the analgesic effect of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) syrup was compared with that of lidocaine 0.03 g/6 g + phenazone (phenyl-dimethylpyrazolone) 0.03 g/6 g (L PDP) ear drops [11].

Biological context of PPM2C

• In intact cells, insulin exposure determined PDP1/2 phosphorylation, which was specifically prevented by PKCdelta antisense [12].
• Decreased PDH activation and glycogenolysis during exercise following fat adaptation with carbohydrate restoration [13].
• OBJECTIVE: The objective of this study was to determine whether down-regulation of pyruvate dehydrogenase phosphatase (PDP) is responsible for poorly active pyruvate dehydrogenase (PDH) in circulating lymphocytes (CLs) of obese subjects (ObS), and if so, whether it improves when their plasma insulin rises [14].
• The catalytic subunit of PDP is a Mg2+-dependent enzyme homologous to the cytosolic phosphatases of the 2C family [15].
• Thus, our results provide the first evidence that there are at least two isoenzymes of PDP in mammals that are different with respect to tissue distribution and kinetic parameters and, therefore, are likely to be different functionally [15].

Anatomical context of PPM2C

• Thus, in muscle and liver cells, insulin causes activation and mitochondrial translocation of PKCdelta, accompanied by PDP phosphorylation and activation [12].
• These observations are consistent with previous findings on the enzymatic parameters of PDP in adipose tissue [15].
• As a result, coordinate changes to PDP activity opposite to those of the other regulatory enzyme, PDH kinase, during food deprivation would maximize the inactivation of skeletal muscle PDH and enhance carbohydrate conservation during periods of limited carbohydrate supply [6].
• Western blot analysis of PDP extracted from mitochondria isolated from liver and skeletal muscle revealed that PDP1 is predominantly expressed in mitochondria from skeletal muscle, whereas PDP2 is much more abundant in the liver rather than muscle mitochondria [15].
• Blot analysis of HeLa cell poly(A)+ RNA showed a single mRNA of 1.8 kb for PDH alpha and 1.7 kb for PDH beta, respectively [9].

Associations of PPM2C with chemical compounds

• During the oral glucose tolerance test, plasma insulin rose considerably more in ObS than in controls; PDHa and PDP1 activity also increased but remained significantly below normal, and PDHt was unvaried in both groups [14].
• Instead, it is sensitive to the biological polyamine spermine, which, in turn, has no effect on the enzymatic activity of PDP1 [15].
• Its activity toward the bovine 32P-labeled pyruvate dehydrogenase complex was Mg(2+)-dependent and Ca(2+)-stimulated and comparable to that of native bovine PDP [16].
• Comparison of the deduced amino acid sequences of the mitochondrial PDPc and the rat cytosolic protein phosphatase 2C indicates that these protein serine/threonine phosphatases evolved from a common ancestor [16].
• The amino acid sequences of NH2-terminal regions of the two subunits of human PDH were highly homologous with those of mature porcine PDH [9].

Physical interactions of PPM2C

• Phosphatases that deactivate CFTR have yet to be identified definitively at the molecular level, however CFTR is regulated by a membrane-bound form of protein phosphatase-2C (PP2C) in several cell types [17].

Enzymatic interactions of PPM2C

• Plasmodium protein phosphatase 2C dephosphorylates translation elongation factor 1beta and inhibits its PKC-mediated nucleotide exchange activity in vitro [18].

Other interactions of PPM2C

• The insulin sensitivity index was calculated, and PDP1 and PDP2 mRNA was sought in the CLs [14].
• Cell cycle regulation and p53 activation by protein phosphatase 2C alpha [19].
• Molecular cloning and characterization of a novel human protein phosphatase 2C cDNA (PP2C epsilon*) [20].
• Regulation of the TAK1 signaling pathway by protein phosphatase 2C [21].
• Intraoocyte injection of 1,2-bis(2-aminophenoxy)ethane-N,N, N,N-tetraacetic acid (BAPTA) or pretreatment of oocytes with BAPTA-acetoxymethyl-ester (BAPTA-AM) nearly completely prevented dephosphorylation of CFTR currents activated by cAMP, an effect consistent with inhibition of protein phosphatase 2C (PP2C) by chelation of intracellular Mg2+ [22].

Analytical, diagnostic and therapeutic context of PPM2C

• In insulin-exposed cells, PDP1/2 activation was paralleled by activation and mitochondrial translocation of PKCdelta, as revealed by cell subfractionation and confocal microscopy studies [12].
• The precursor proteins of PDH alpha and PDH beta were detected by immunoprecipitation from an 35S-labeled cell-free translation system [9].
• The free peptide 167-184 LA inhibited the ELISA reaction of PBC antibodies to PDH and totally abolished the typical immunofluorescence reaction of PBC sera on rat kidney, stomach and liver, or human HEp-2 cell substrates [23].
• An abscisic acid (ABA)-induced cDNA fragment encoding a putative protein phosphatase 2C (PP2C) was obtained by means of differential reverse transcriptase-polymerase chain reaction approach [24].
• Because of the difficulty in translating the mathematical analysis of various compartments into the biological model, biodistribution was monitored by a gamma camera linked to a DEC PDP 11/34 computer system [25].

References