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Your search keyword '"Phospholipase C delta"' showing total 3 results
Start Over Descriptor "Phospholipase C delta" Publisher escholarship, university of california
3 results on '"Phospholipase C delta"'

1. Genome-wide association study identifies eight loci associated with blood pressure

Author

Newton-Cheh, Christopher, Johnson, Toby, Gateva, Vesela, Tobin, Martin D, Bochud, Murielle, Coin, Lachlan, Najjar, Samer S, Zhao, Jing Hua, Heath, Simon C, Eyheramendy, Susana, Papadakis, Konstantinos, Voight, Benjamin F, Scott, Laura J, Zhang, Feng, Farrall, Martin, Tanaka, Toshiko, Wallace, Chris, Chambers, John C, Khaw, Kay-Tee, Nilsson, Peter, van der Harst, Pim, Polidoro, Silvia, Grobbee, Diederick E, Onland-Moret, N Charlotte, Bots, Michiel L, Wain, Louise V, Elliott, Katherine S, Teumer, Alexander, Luan, Jian'an, Lucas, Gavin, Kuusisto, Johanna, Burton, Paul R, Hadley, David, McArdle, Wendy L, Brown, Morris, Dominiczak, Anna, Newhouse, Stephen J, Samani, Nilesh J, Webster, John, Zeggini, Eleftheria, Beckmann, Jacques S, Bergmann, Sven, Lim, Noha, Song, Kijoung, Vollenweider, Peter, Waeber, Gerard, Waterworth, Dawn M, Yuan, Xin, Groop, Leif, Orho-Melander, Marju, Allione, Alessandra, Di Gregorio, Alessandra, Guarrera, Simonetta, Panico, Salvatore, Ricceri, Fulvio, Romanazzi, Valeria, Sacerdote, Carlotta, Vineis, Paolo, Barroso, Inês, Sandhu, Manjinder S, Luben, Robert N, Crawford, Gabriel J, Jousilahti, Pekka, Perola, Markus, Boehnke, Michael, Bonnycastle, Lori L, Collins, Francis S, Jackson, Anne U, Mohlke, Karen L, Stringham, Heather M, Valle, Timo T, Willer, Cristen J, Bergman, Richard N, Morken, Mario A, Döring, Angela, Gieger, Christian, Illig, Thomas, Meitinger, Thomas, Org, Elin, Pfeufer, Arne, Wichmann, H Erich, Kathiresan, Sekar, Marrugat, Jaume, O'Donnell, Christopher J, Schwartz, Stephen M, Siscovick, David S, Subirana, Isaac, Freimer, Nelson B, Hartikainen, Anna-Liisa, McCarthy, Mark I, O'Reilly, Paul F, Peltonen, Leena, Pouta, Anneli, de Jong, Paul E, Snieder, Harold, van Gilst, Wiek H, Clarke, Robert, Goel, Anuj, Hamsten, Anders, and Peden, John F

Subjects
Biological Sciences, Genetics, Hypertension, Cardiovascular, Prevention, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Adaptor Proteins, Signal Transducing, Blood Pressure, Cardiovascular Diseases, Chromosome Mapping, Cytochrome P-450 CYP1A2, DNA-Binding Proteins, Diastole, Europe, Fibroblast Growth Factor 5, Genetic Variation, Genome-Wide Association Study, Humans, India, Intracellular Signaling Peptides and Proteins, Methylenetetrahydrofolate Reductase (NADPH2), Open Reading Frames, Phospholipase C delta, Polymorphism, Single Nucleotide, Proteins, Steroid 17-alpha-Hydroxylase, Systole, White People, Wellcome Trust Case Control Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Published
2009

2. Group IV Cytosolic Phospholipase A2 Binds with High Affinity and Specificity to Phosphatidylinositol 4,5-Bisphosphate Resulting in Dramatic Increases in Activity*

Author

Mosior, Marian, Six, David A, and Dennis, Edward A

Subjects
Biochemistry and Cell Biology, Biological Sciences, Generic health relevance, Amino Acid Sequence, Animals, Binding Sites, Blood Proteins, Humans, Isoenzymes, Kinetics, Liposomes, Micelles, Molecular Sequence Data, Phosphatidylethanolamines, Phosphatidylinositol 4, 5-Diphosphate, Phosphatidylserines, Phospholipase C delta, Phospholipases A, Phospholipases A2, Phosphoproteins, Rabbits, Recombinant Proteins, Spectrin, Type C Phospholipases, Chemical Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

The group IV cytosolic phospholipase A2 (cPLA2) exhibits a potent and specific increase in affinity for lipid surfaces containing phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) at physiologically relevant concentrations. Specifically, the presence of 1 mol% PtdIns(4,5)P2 in phosphatidylcholine vesicles results in a 20-fold increase in the binding affinity of cPLA2. This increased affinity is accompanied by an increase in substrate hydrolysis of a similar magnitude. The binding studies and kinetic analysis indicate that PtdIns(4,5)P2 binds to cPLA2 in a 1:1 stoichiometry. The magnitude of the effect of PtdIns(4,5)P2 is unique among anionic phospholipids and larger than that for other polyphosphate phosphatidylinositols. The effect of PtdIns(4,5)P2 on the activity of cPLA2 is at least an order of magnitude larger than the concomitant changes in the fraction of the enzyme associated with lipid membranes. Striking parallels between the interaction of cPLA2 with PtdIns(4,5)P2 and the interaction of the pleckstrin homology domain of phospholipase C delta 1 with PtdIns(4,5)2 combined with sequence analysis of cPLA2 lead us to propose the existence and location of a pleckstrin homology domain in cPLA2. We further show that the very nature of the interaction of proteins such as cPLA2 with multiple ligands incorporated into membranes follows a specific model which necessitates the use of an experimental methodology suitable for a membrane interface to allow for a meaningful analysis of the data.

Published
1998

3. Group IV cytosolic phospholipase A2 binds with high affinity and specificity to phosphatidylinositol 4,5-bisphosphate resulting in dramatic increases in activity.

Author

Mosior, M, Mosior, M, Six, DA, Dennis, EA, Mosior, M, Mosior, M, Six, DA, and Dennis, EA

Abstract

The group IV cytosolic phospholipase A2 (cPLA2) exhibits a potent and specific increase in affinity for lipid surfaces containing phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) at physiologically relevant concentrations. Specifically, the presence of 1 mol% PtdIns(4,5)P2 in phosphatidylcholine vesicles results in a 20-fold increase in the binding affinity of cPLA2. This increased affinity is accompanied by an increase in substrate hydrolysis of a similar magnitude. The binding studies and kinetic analysis indicate that PtdIns(4,5)P2 binds to cPLA2 in a 1:1 stoichiometry. The magnitude of the effect of PtdIns(4,5)P2 is unique among anionic phospholipids and larger than that for other polyphosphate phosphatidylinositols. The effect of PtdIns(4,5)P2 on the activity of cPLA2 is at least an order of magnitude larger than the concomitant changes in the fraction of the enzyme associated with lipid membranes. Striking parallels between the interaction of cPLA2 with PtdIns(4,5)P2 and the interaction of the pleckstrin homology domain of phospholipase C delta 1 with PtdIns(4,5)2 combined with sequence analysis of cPLA2 lead us to propose the existence and location of a pleckstrin homology domain in cPLA2. We further show that the very nature of the interaction of proteins such as cPLA2 with multiple ligands incorporated into membranes follows a specific model which necessitates the use of an experimental methodology suitable for a membrane interface to allow for a meaningful analysis of the data.

Published
1998

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