The mechanisms of growth factor action were studied in a fibroblastic cell line capable of reversible growth arrest in G0-G1. This cell line, derived from Chinese hamster lung, can be stimulated to divide by a limited set of purified growth factors, including EGF, FGF, PDGF, x-thrombin (THR), serotonin (5-HT) and insulin. THR and 5-HT stimulate, via a G-protein (Gp), a polyphosphoinositide-specific phospholipase C (PtdIns(4,5)P2-PLC). In contrast, the mitogens EGF, FGF, PDGF, and insulin do not stimulate PtdIns(4,5)P2-PLC, unless this pathway has been preactivated by THR or AIF4. Finally, from the specific inhibitory action of pertussis toxin on THR- and 5-HT-induced DNA synthesis, and from the exploitation of the 5-HT pharmacological tools, we conclude that: (i) there are at least two distinct Gproteins involved in signalling growth: Gp, coupling receptors to PtdIns(4,5)P2-PLC, and G1 coupling receptors negatively to adenylyl cyclase and probably to other unknown effector(s); (ii) activation of ...
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DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3-phosphodiester bond, giving rise to DNA with a free 3 phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3-phosphoglycolates on protruding 3 ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3exonuclease activity and can remove a single nucleoside from the 3end of DNA and RNA molecules with 3hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3phosphate ...
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Zinc atom in PDB 1tbf: Catalytic Domain of Human Phosphodiesterase 5A in Complex With Sildenafil
BioAssay record AID 476074 submitted by ChEMBL: Inhibition of human Tdp1 expressed in Escherichia coli assessed as blockade of enzyme-mediated hydrolysis of phosphodiester linkage between tyrosine and double stranded DNA substrate bearing blunt end by SDS-PAGE electrophoresis.
Camptothecin (CPT) and its derivatives (e.g. Irinotecan) are commonly used anticancer drugs which increase the half-life of topoisomerase I (Top1) cleavage complexes (Top1cc) during the Top1 catalytic cycle. Even in the presence of CPT Top1 will eventually remove itself by resuming its catalytic cycle. However, increasing Top1cc half-life also increases the probability of transcription and/or replication encounters with the transient Top1cc, which can lead to double-strand breaks, highly cytotoxic for the cells. Tyrosyl-DNA phosphodiesterase 1 (Tdp1) and Mre11 nuclease activity have been suggested to have a role in the removal of Top1 in the context of transcription and replication respectively. Also, Swi10ERCC1-Rad16XPF has been shown to act as a redundant pathway with Tdp1 for the repair of Top1-mediated DNA damage. To understand the interaction among Top1 removal pathways I have performed a genome-wide study of Top1cc removal from replicating and transcribing DNA in WT, mre11, tdp1 and ...
Complete information for TDP1 gene (Protein Coding), Tyrosyl-DNA Phosphodiesterase 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994 ...
Cell structureCell envelopeBiosynthesis and degradation of surface polysaccharides and lipopolysaccharidesundecaprenyl-phosphate alpha-N-acetylglucosaminyl 1-phosphatetransferase (TIGR02380; EC 2.7.8.33; HMM-score: 152) ...
Abstract: Systems with random fluctuations are ubiquitous in the real world. Stochastic PDEs are default models for these random systems, just as PDEs are default models for deterministic systems. However, a large class of such stochastic PDEs were poorly understood until very recently: the presence of very singular random forcing as well as nonlinearities render it challenging to interpret what one even means by a ``solution. The recent breakthroughs by M. Hairer, M. Gubinelli and other researchers including the speaker not only established solution theories for these singular SPDEs, but also led to an explosion of new questions. These include scaling limits of random microscopic models, development of numerical schemes, ergodicity of random dynamical systems and a new approach to quantum field theory. In this talk we will discuss the main ideas of the recent solution theories of singular SPDEs, and how these SPDEs arise as limits of various important physical models ...
Abstract: Systems with random fluctuations are ubiquitous in the real world. Stochastic PDEs are default models for these random systems, just as PDEs are default models for deterministic systems. However, a large class of such stochastic PDEs were poorly understood until very recently: the presence of very singular random forcing as well as nonlinearities render it challenging to interpret what one even means by a ``solution. The recent breakthroughs by M. Hairer, M. Gubinelli and other researchers including the speaker not only established solution theories for these singular SPDEs, but also led to an explosion of new questions. These include scaling limits of random microscopic models, development of numerical schemes, ergodicity of random dynamical systems and a new approach to quantum field theory. In this talk we will discuss the main ideas of the recent solution theories of singular SPDEs, and how these SPDEs arise as limits of various important physical models ...
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 is an enzyme that in humans is encoded by the ENPP1 gene. This gene is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleotides and nucleotide sugars. This protein may function to hydrolyze nucleoside 5 triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates. Mutations in this gene have been associated with Idiopathic infantile arterial calcification, ossification of the posterior longitudinal ligament of the spine (OPLL), and insulin resistance. Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been shown to interact with Insulin receptor. GRCh38: Ensembl release 89: ...
Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (E-NPP 2), is an enzyme that in humans is encoded by the ENPP2 gene. Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (NPP2 or ENPP2), is a secreted enzyme important for generating the lipid signaling molecule lysophosphatidic acid (LPA). Autotaxin has lysophospholipase D activity that converts lysophosphatidylcholine into LPA. Autotaxin was originally identified as a tumor cell-motility-stimulating factor; later it was shown to be LPA (which signals through lysophospholipid receptors), the lipid product of the reaction catalyzed by autotaxin, which is responsible for its effects on cell-proliferation. The protein encoded by this gene functions as a phosphodiesterase. Autotaxin is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants have been identified. Autotaxin is able to cleave the phosphodiester bond between ...
OBJECTIVE-A recent meta-analysis demonstrated a nominal association of the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K→Q missense single nucleotide polymorphism (SNP) at position 121 with type 2 diabetes. We set out to confirm the association of ENPP1 K121Q with hyperglycemia, expand this association to insulin resistance traits, and determine whether the association stems from K121Q or another variant in linkage disequilibrium with it. RESEARCH DESIGN AND METHODS-We characterized the haplotype structure of ENPP1 and selected 39 tag SNPs that captured 96% of common variation in the region (minor allele frequency ≥5%) with an r2 value ≥0.80. We genotyped the SNPs in 2,511 Framingham Heart Study participants and used age- and sex-adjusted linear mixed effects (LME) models to test for association with quantitative metabolic traits. We also examined whether interaction between K121Q and BMI affected glycemic trait levels. RESULTS-The Q allele of K121Q (rs1044498) was ...
Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder that is frequently fatal in infancy. This disorder is characterized by calcification of large and medium sized arteries and myointimal proliferation resulting in arterial stenosis. In some affected individuals the disease is detected prenatally. Most patients die in early infancy due to myocardial infarction or congestive heart failure. GACI1 (MIM 208000) is caused by loss of function mutations in the ectonucleotide pyrophosphatase / phosphodiesterase 1 gene (ENPP1) and GACI2 (MIM 614473) is caused by loss of function mutations in the ATP-binding cassette, subfamily c, member 6 gene (ABCC6). ENPP1 is a transmembrane glycoprotein involved in the regulation of soft issue calcification and bone and joint cartilage mineralization via the generation of pyrophosphate (PPi). PPi is a physiological inhibitor of hydroxyapatite formation and a suppressor of chondrogenesis. ABCC6 is an ATP-binding cassette transmembrane ...
ENPP1 antibody [N2C2], Internal (ectonucleotide pyrophosphatase/phosphodiesterase 1) for WB. Anti-ENPP1 pAb (GTX103447) is tested in Human samples. 100% Ab-Assurance.
An ecto-nucleotide pyrophosphatase modulates purineceptor-mediated signal transduction and is inhibited by purinereceptor antagonists ...
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Clone FR3-16A11 recognizes CD203c, a glycosylated type II transmembrane molecule that belongs to the family of ecto-nucleotide pyrophosphatase/ phosphodiesterase (E-NPP3) enzymes. Among hematopoietic cells, expression of CD203c is restricted to basophils as well as to mast cells and their precursors, and has been described as specific for this lineage. Protein and/or mRNA expression of CD203c has also been found in solid tissues such as uterus or prostate. Basophils and mast cells are key producers of mediators that drive the onset of inflammatory responses, e.g., in allergy. Allergen challenge leads to a rapid up-regulation of activation markers such as CD203c or CD63. Due to its restricted expression pattern, CD203c is discussed as a specific marker to monitor the allergen-induced activation of basophils, e.g., in flow cytometric basophil activation tests of the peripheral blood. - Great Britain
Clone FR3-16A11 recognizes CD203c, a glycosylated type II transmembrane molecule that belongs to the family of ecto-nucleotide pyrophosphatase/ phosphodiesterase (E-NPP3) enzymes. Among hematopoietic cells, expression of CD203c is restricted to basophils as well as to mast cells and their precursors, and has been described as specific for this lineage. Protein and/or mRNA expression of CD203c has also been found in solid tissues such as uterus or prostate. Basophils and mast cells are key producers of mediators that drive the onset of inflammatory responses, e.g., in allergy. Allergen challenge leads to a rapid up-regulation of activation markers such as CD203c or CD63. Due to its restricted expression pattern, CD203c is discussed as a specific marker to monitor the allergen-induced activation of basophils, e.g., in flow cytometric basophil activation tests of the peripheral blood. - Lëtzebuerg
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Zinc atom in PDB 3frg: Catalytic Domain of Human Phosphodiesterase 4B2B in Complex With A Quinoline Inhibitor
Bone has emerged as an important endocrine regulator that can mediate the interplay between bone remodelling and energy metabolism. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) is a factor that regulates bone mineralisation and is elevated in individuals with insulin resistance, a condition associated with type 2 and obesity-related diabetes. Thus, this factor might play a role in the development of metabolic disease. Vicky MacRae and colleagues sought to investigate this by using Enpp−/− mice, which lack NPP1 and exhibit impaired bone metabolism. These mice showed a pronounced resistance to obesity and to the development of insulin resistance in response to chronic high-fat feeding. Moreover, Enpp1−/− mice exhibited increased levels of the bone-derived hormone osteocalcin, which increases β-cell proliferation and insulin secretion, thereby linking bone remodelling to metabolic homeostasis. These results support the involvement of NPP1 in the development of obesity and type ...
The phosphodiesterases (PDEs) are metal ion-dependent enzymes that regulate cellular signaling by metabolic inactivation of the ubiquitous second messengers cAMP and cGMP. In this role, the PDEs are involved in many biological and metabolic processes and are proven targets of successful drugs for the treatments of a wide range of diseases. However, because of the rapidity of the hydrolysis reaction, an experimental knowledge of the enzymatic mechanisms of the PDEs at the atomic level is still lacking. Here, we report the structures of reaction intermediates accumulated at the reaction steady state in PDE9/crystal and preserved by freeze-trapping. These structures reveal the catalytic process of a PDE and explain the substrate specificity of PDE9 in an actual reaction and the cation requirements of PDEs in general. Structural basis for the catalytic mechanism of human phosphodiesterase 9.,Liu S, Mansour MN, Dillman KS, Perez JR, Danley DE, Aeed PA, Simons SP, Lemotte PK, Menniti FS Proc Natl Acad ...
The ability of cells to detect and respond to nucleotide signals in the local microenvironment is essential for vascular homeostasis. The enzyme ectonucleotide tri(di)phosphohydrolase-1 (ENTPD1, also known as CD39) on the surface of leukocytes and endothelial cells metabolizes locally released, intravascular ATP and ADP, thereby eliminating these prothrombotic and proinflammatory stimuli. Here, we evaluated the contribution of CD39 to atherogenesis in the apolipoprotein E-deficient (ApoE-deficient) mouse model of atherosclerosis. Compared with control ApoE-deficient animals, plaque burden was markedly increased along with circulating markers of platelet activation in ...
PDE8B - PDE8B (untagged)-Human phosphodiesterase 8B (PDE8B), transcript variant 2 available for purchase from OriGene - Your Gene Company.
2010 05 09.49510 16 02 32.319 +00 26 09.90 21.6G 523713 F51 C~2kQ9 2010 05 11.55939 16 02 21.787 +00 27 10.99 21.7G 523713 F51 C~2kQ9 2010 06 04.37125 16 00 17.562 +00 35 55.78 21.2G 523713 F51 C~2kQ9 2010 07 30.25674 15 56 56.215 +00 32 00.64 21.5G 523713 F51 C~2kQ9 2011 04 30.53662 16 11 13.046 +00 40 04.81 21.2G 523713 F51 C~2kQ9 2011 04 30.53721 16 11 13.027 +00 40 04.99 21.5G 523713 F51 C~2kQ9 2011 05 11.45580 16 10 19.732 +00 45 55.88 20.8G 523713 F51 C~2kQ9 2011 05 11.46786 16 10 19.659 +00 45 56.62 21.9G 523713 F51 C~2kQ9 2012 05 16.47132 16 17 46.315 +01 07 29.79 21.5G 523713 F51 C~2kQ9 2012 05 16.48549 16 17 46.236 +01 07 30.20 21.9G 523713 F51 C~2kQ9 2012 05 16.49963 16 17 46.159 +01 07 30.59 21.8G 523713 F51 C~2kQ9 2012 06 15.38824 16 15 10.670 +01 15 45.53 21.7G 523713 F51 C~2kQ9 2012 06 15.40187 16 15 10.610 +01 15 45.54 21.8G 523713 F51 C~2kQ9 2012 06 15.41549 16 15 10.542 +01 15 45.80 21.3G 523713 F51 C~2kQ9 2012 06 15.42921 16 15 10.463 +01 15 45.77 21.4G 523713 F51 C~2kQ9 2013 ...
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ENPP7兔多克隆抗体(ab121827)可与人样本反应并经IHC实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
不動産担保ローンは無担保のローンに比べ金利が安い - 所有している不動産を担保にして借り入れをする不動産担保ローンは 無担保のローンに比べると 不動産の価値にもよりますが 金利が安く 融資額が大きい 長期の借り入れが可能などのメリットがあります》 融資額の内容は所有している […] ...
1. A simple new assay for glycerylphosphorylcholine phosphodiesterase is described, in which radioactive glycerylphosphorylcholine is used as substrate and the reaction products are separated by adsorption on an anion-exchange resin. 2. Rat liver subcellular fractions contained both particulate (58%) and soluble (42%) glycerylphosphorylcholine phosphodiesterase. Both activities released free choline from glycerylphosphorylcholine. 3. The particulate glycerylphosphorylcholine phosphodiesterase was recovered mainly in the nuclear and microsomal fractions and showed a distribution similar to those of 5′-nucleotidase and alkaline phosphodiesterase I, both of which are constituents of the liver plasma membrane. 4. During purification of plasma membranes glycerylphosphorylcholine phosphodiesterase, 5′-nucleotidase and alkaline phosphodiesterase I showed largely similar behaviour, indicating that glycerylphosphorylcholine phosphodiesterase is also localized in liver plasma membranes. Slight ...
This family consists of phosphodiesterases, including human plasma-cell membrane glycoprotein PC-1 / alkaline phosphodiesterase I / nucleotide pyrophosphatase (nppase). These enzymes catalyse the cleavage of phosphodiester and phosphosulphate bonds in NAD, deoxynucleotides and nucleotide sugars [(PUBMED:9344668)]. Another member of this family is ATX an autotaxin, tumor cell motility-stimulating protein which exhibits type I phosphodiesterases activity [(PUBMED:7982964)]. The alignment encompasses the active site [(PUBMED:7730366), (PUBMED:7982964)]. Also present within this family is 60 kDa Ca2+-ATPase from Myroides odoratus [(PUBMED:8617788)].. This signature also hits a number of ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis.. ...
Haemophilus influenzae outer membrane protein D (PD) is a glycerophosphodiester phosphodiesterase (GlpQ) activity-possessing virulence factor and a promising vaccine antigen, providing 35.3% efficacy against acute otitis media caused by nontypeable H. influenzae (NTHI) when it was used as a carrier protein in a novel pneumococcal PD conjugate (Pnc-PD) vaccine. To study if PD-induced protection against NTHI could be due to antibodies that inhibit or neutralize its enzymatic activity, a GlpQ enzyme inhibition assay was developed, and serum samples collected from Finnish infants before and after Pnc-PD vaccination were analyzed for enzyme inhibition and anti-PD immunoglobulin G (IgG) antibody concentration. Before vaccination at age 2 months, the majority (84%) of infants (n = 69) had no detectable anti-PD IgG antibodies, and all were enzyme inhibition assay negative (inhibition index, ,20). At age 13 to 16 months, all infants receiving three or four doses of Pnc-PD had detectable anti-PD IgG ...
DNA double-strand breaks (DSBs) containing unligatable termini are potent cytotoxic lesions leading to growth arrest or cell death. The Artemis nuclease and tyrosyl-DNA phosphodiesterase (TDP1) are each capable of resolving protruding 3′-phosphoglycolate (PG) termini of DNA double-strand breaks (DSBs). Consequently, a knockout of Artemis and a knockout/knockdown of TDP1 rendered cells sensitive to the radiomimetic agent neocarzinostatin (NCS), which induces 3′-PG-terminated DSBs. Unexpectedly, however, a knockdown or knockout of TDP1 in Artemis-null cells did not confer any greater sensitivity than either deficiency alone, indicating a strict epistasis between TDP1 and Artemis. Moreover, a deficiency in Artemis, but not TDP1, resulted in a fraction of unrepaired DSBs, which were assessed as 53BP1 foci. Conversely, a deficiency in TDP1, but not Artemis, resulted in a dramatic increase in dicentric chromosomes following NCS treatment. An inhibitor of DNA-dependent protein kinase, a key regulator
During development, oligodendrocytes (OLGs), the myelinating cells of the central nervous system (CNS), undergo a stepwise progression during which OLG progenitors, specified from neural stem/progenitor cells, differentiate into fully mature myelinating OLGs. This progression along the OLG lineage is characterized by well-synchronized changes in morphology and gene expression patterns. The studies presented in this dissertation identified the extracellular factor Autotaxin (ATX) as a novel upstream signal modulating HDAC1/2 activity and gene expression in cells of the OLG lineage. Using the zebrafish as an in vivo model system, as well as rodent primary OLG cultures, this functional property of ATX was found to be mediated by its lysoPLD activity, which has been well-characterized to generate the lipid signaling molecule lysophosphatidic acid (LPA). LPA binds to Gprotein-coupled LPA receptors (LPARs) on the surface of OLGs to initiate downstream signaling events. ATXs lysoPLD activity was found to
The CD203c molecule is a type II transmembrane protein that belongs to the ectonucleotide pyrophosphatase / phosphosdiesterase 3 (E-NPP3) family of enzymes involved in hydrolysis of oligonucleotides, nucleoside phosphates, and NAD.
Description: Secreted human β isoform (teratocarcinoma derived) autotaxin with C-terminal 6-His tag was expressed in Sf9 cells and purified using nickel-NTA chromatography ...
cAMP PDEs are emerging as a promising class of drug targets in asthma and cardiovascular disease therapeutic areas. HDB has established the cell-based screening assay for cAMP phosphodiesterase (PDE) inhibitors in HDB based on the Codex ACTOne™ technology. The specificity of the assay has been verified by known PDE inhibitors. Only PDE4 and pan-PDE inhibitors showed positive signals in the cell line that was optimized ...
Recombinant human ENPP1 Protein is a 840 amino acid protein expressed in HEK293. Tested applications are: Cell culture and/or animal studies, Western blotting, ELISA.
K20R, K43Q, E44D, K101KQ, V118I, K122E, K166R, V179VI, G196GE, T200A, Q207E, H208HFLY, R211K, V245E, E248Q, D250E, K277R, Q278H, I293V, K347KQ, A360T, K366R, T369V, A376T, K390KR, ...
V35T, T39A, E44ED, V60I, K101KQ, V118VI, K122E, I135T, S162SDGN, H208HY, R211RK, K223KQ, V245VE, A272P, K277R, T286A, E297A, M357K, I375V, A400T, V435E, D460N, R461K, T470A, L491S, Q524E, Q547R, ...
The status of each map region is indicated by a symbol, which describes the type of feature, and a colour, which indicates the completeness of that feature in a map region. ...
Sigma-Aldrich offers abstracts and full-text articles by [Marcelo L Santoro, Tais S Vaquero, Adriana F Paes Leme, Solange M T Serrano].
Hypophosphatemic rickets, autosomal recessive, 1 (ARHR1; MIM 241520) is caused by mutations in the dentin matrix acidic phosphoprotein 1 gene (DMP1) and hypophosphatemic rickets, autosomal recessive, 2 (ARHR2; MIM 613312) is caused by mutations in the ectonucleotide pyrophosphatase / phosphodiesterase 1 gene (ENPP1). DMP1 is a highly acidic, serine rich protein critical for osteocyte maturation. Several loss of function mutations have been described in DMP1. ENPP1 is a transmembrane glycoprotein regulating soft tissue calcification and bone and joint cartilage mineralization via generation of pyrophosphate (PPi). PPi is a physiological inhibitor of hydroxyapatite crystal formation and a suppressor of chondrogenesis. Loss of function mutations have also been described in ENPP1. Mutations in ENPP1 also cause generalized arterial calcification of infancy 1 (GACI1; MIM 208000). In at least one instance, the identical homozygous ENPP1 mutation has been shown to cause hypophosphatemic rickets in a ...
Definition of 2,3-cyclic-nucleotide phosphodiesterases in the Definitions.net dictionary. Meaning of 2,3-cyclic-nucleotide phosphodiesterases. What does 2,3-cyclic-nucleotide phosphodiesterases mean? Information and translations of 2,3-cyclic-nucleotide phosphodiesterases in the most comprehensive dictionary definitions resource on the web.
Type 2 diabetes mellitus is a chronic disease characterised by progressive insulin resistance and loss of β-cell function. An incomplete understanding of its pathogenesis is hindering the effective treatment of this disease. Roux-en Y gastric bypass surgery (RYGB); however, causes rapid remission of liver insulin resistance and type 2 diabetes, and therefore affords us an opportunity to examine some fundamental characteristics of these conditions. Gathering evidence suggests that liver insulin resistance may be a crucial contributor to development of diabetes. In this thesis, we used liver biopsies taken before, and in some individuals after, RYGB surgery to explore or identify several molecular processes involved in the pathogenesis of type 2 diabetes. The study cohort included individuals with normal glucose tolerance and others with type 2 diabetes. Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) may cause insulin resistance through its inhibitory action on insulin signalling. ...
To examine the relationship of clone 71 to the putative LPA receptor, an 18-mer antisense oligonucleotide with the sequence of 5′-ATTGTCTAGGGCAGTATT-3′, complementary to the putative N-terminal 5-11 amino acids, was synthesized and injected into Xenopus oocytes. A sense- and a random-sequence oligonucleotide, containing the same relative percentages of the four nucleotides, served as controls. Oscillatory Cl− currents elicited by LPA and cLPA measured with standard two-electrode voltage-clamp recording in the three groups of oligonucleotide-injected oocytes (Fig. 1d) showed no statistically significant differences in the response to cLPA nor were there any differences seen in the oocytes injected with distilled water. In contrast, the LPA response was substantially diminished, by 68 ± 12%, in the group injected with as little as 0.3 fmol of the antisense oligonucleotide. Oocytes injected with sense and nonsense oligonucleotides showed LPA responses similar to those of sham-injected ...
The lysophospholipase D (autotaxin, ATX) plays an important role in cancer invasion, metastasis, tumor progression, tumorigenesis, neuropathic pain, fibrotic diseases, cholestatic pruritus, lymphocyte homing, and thrombotic diseases by producing the lipid mediator lysophosphatidic acid (LPA). A high-throughput screen of ATX inhibition using the lysophosphatidylcholine (LPC) -like substrate fluorogenic substrate 3 (FS-3) and ~10,000 compounds from the University of Cincinnati Drug Discovery Center (UC DDC) identified several small-molecule inhibitors with IC50 values ranging from nanomolar to low micromolar. The pharmacology of the three most potent compounds, 918013 (1), 931126 (2), and 966791 (3) were further characterized in enzyme, cellular, and whole animal models. Compounds 1 and 2 were competitive inhibitors of ATX-mediated hydrolysis of the lysophospholipase substrate FS-3. In contrast, compound 3 was a competitive inhibitor of both FS-3 and the phosphodiesterase substrate p-nitrophenyl ...
The IUPHAR/BPS Guide to Pharmacology. phosphodiesterase 4D - Phosphodiesterases, 3,5-cyclic nucleotide (PDEs). Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a high affinity for both cAMP and cGMP.
Purification and properties of phosphatidylinositol-specific phospholipase C of Bacillus thuringiensis.: A phosphatidylinositol-specific phospholipase C was pur