Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A full-length cDNA encoding a novel human protein phosphatase 1 (PP1) binding subunit of molecular mass 36 kDa, termed PPP1R5, was sequenced. PPP1R5 shows 42% identity to the glycogen binding subunit (G(L)) of PP1 from rat liver and 28% identity to the N-terminal region of the glycogen binding subunit (G(M)) of PP1 from human skeletal muscle. Like G(L), PPP1R5 modulates the specificity of PP1, but it differs from G(L) in being present in a wide variety of tissues, besides liver. The amino acid sequence and properties of PPP1R5 indicate that it is not subject to the same modes of covalent and allosteric regulation by hormones as are G(M) and G(L).
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PMID:Amino acid sequence of a novel protein phosphatase 1 binding protein (R5) which is related to the liver- and muscle-specific glycogen binding subunits of protein phosphatase 1. 898 75

A complementary DNA encoding a novel human protein phosphatase 1 (PP1) glycogen-targetting subunit of molecular mass 33 kDa has been sequenced. PPP1R6 is 31% identical to the glycogen-targetting subunit (G(L)) of PP1 from rat liver, 28% identical to the N-terminal region of the glycogen-targetting subunit (G(M)) from human skeletal muscle and 27% identical to glycogen-targetting subunit PPP1R5. Unlike human PPP1R5 and its murine homologue PTG, whose mRNAs are most abundant in skeletal muscle, heart and liver, PPP1R6 is present at similar levels in a wide variety of tissues. The PPP1R6 is associated with glycogen in muscle but is not subject to the same modes of covalent and allosteric regulation as G(M) and G(L).
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PMID:PPP1R6, a novel member of the family of glycogen-targetting subunits of protein phosphatase 1. 941 28

Protein targeting to glycogen (PTG), also known as PPP1R5, is a widely expressed member of a growing family of proteins that target protein phosphatase-1 (PP-1) to glycogen particles. Because PTG also binds to glycogen synthase and phosphorylase kinase, it has been suggested that it serves as a "scaffold" for efficient activation of glycogen synthesis. However, very little is known about the metabolic effects of PTG. In this study, we have used recombinant adenovirus to overexpress PTG in primary rat hepatocytes, a cell type with high glycogenic capacity. We find that overexpression of PTG potently activates glycogen synthesis in cultured hepatocytes. Surprisingly, the glycogenic effect of PTG is observed even in the complete absence of carbohydrates or insulin in the culture medium. Furthermore, glycogenolytic agents such as forskolin or glucagon are largely ineffective at activating glycogen degradation in PTG overexpressing hepatocytes, even though large increases in cAMP levels are demonstrated. These metabolic effects of PTG overexpression are accompanied by a 3.6-fold increase in glycogen synthase activation state and a 40% decrease in glycogen phosphorylase activity. Our results are consistent with a model in which PTG overexpression "locks" the hepatocyte in a glycogenic mode, presumably via its ability to promote interaction of enzymes of glycogen metabolism with PP-1.
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PMID:Overexpression of protein targeting to glycogen (PTG) in rat hepatocytes causes profound activation of glycogen synthesis independent of normal hormone- and substrate-mediated regulatory mechanisms. 975 75

Recent studies have revealed that genetic alterations of the protein phosphatase genes, including PTEN, PPP2R1A, PPP2R1B and PPP1R3, are involved in human carcinogenesis. In the present study, we examined the genetic and expression status of nine protein phosphatase 1 (PP1) genes in 55 human cancer cell lines, consisting of 10 small cell lung cancers, 22 non-small cell lung cancers, 11 colorectal cancers, 7 gastric cancers and 5 ovarian cancers. The PP1 genes examined were three catalytic subunit genes, PPP1CA, PPP1CB and PPP1CC, and six regulatory subunit genes, PPP1R1A, PPP1R2, PPP1R5, PPP1R6, PPP1R7 and PPP1R8. Three catalytic subunit genes and three regulatory subunit genes, PPP1R2, PPP1R7 and PPP1R8, were ubiquitously expressed in the 55 cell lines, while PPP1R1A, PPP1R5, and PPP1R6 were differentially expressed. Possible missense mutations of the PPP1R5, PPP1R7 and PPP1R8 genes were detected in one (2%), two (4%) and one (2%) cell line, respectively. A rare, non-synonymous polymorphism was also identified in the PPP1R5 gene. Four of the 55 cell lines carried genetic alterations of several protein phosphatase genes, including PTEN, PPP1R3, PPP1R7 and PPP1R8. Ubiquitous expression as well as a lack of genetic diversity of catalytic subunit genes suggested the essential role of these genes for the growth of cancer cells. In contrast, differential expression, somatic mutations and/or genetic polymorphisms of several regulatory subunit genes indicate the involvement of these genes in multistep carcinogenesis.
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PMID:Genetic alterations and expression of the protein phosphatase 1 genes in human cancers. 1125 Nov 79

When the association between a ligand immobilized on a membrane disk and a fluorescence-labeled analyte was monitored with a fluorescent microplate reader, the time-dependent increase in fluorescence intensity of the reaction mixture was observed. A novel assay system for the specific interaction based on this phenomenon was designated the homogeneous assay for fluorescence concentrated on membrane (HAFCOM). In this study, streptococcal protein G (SpG) and glycogen-binding subunit R5 of protein phosphatase 1 (PPP1R5) tagged by green fluorescent protein (GFP) were used as the fluorescence-labeled analytes, and the affinity change caused by various amino acid substitutions was measured with HAFCOM. From the site-directed mutagenesis of SpG and PPP1R5, it was clarified that (i) the association rate constant of the Lys454Pro/Glu456Gln mutant of SpG to goat immunoglobulin G was almost equivalent to that of the wild-type but its dissociation rate constant was about 2.7 times that of the wild-type and (ii) the amino acid substitutions of Phe180 in PPP1R5 reduced glycogen-binding by 30-50%. Since HAFCOM using the GFP-tagged analyte requires no special chemicals and instruments, this system can easily and economically assay the specific interaction between target protein and ligand.
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PMID:A homogeneous assay for relative affinity of binding proteins using a green fluorescent protein tag and membrane disk. 1604 12