Genomes and Genes
Gene Symbol: PDE4D
Description: phosphodiesterase 4D
Alias: ACRDYS2, DPDE3, HSPDE4D, PDE43, PDE4DN2, STRK1, cAMP-specific phosphodiesterase PDE4D6, phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila)
Publications158 found, 100 shown here
- Differential distribution of PDE4D splice variant mRNAs in rat brain suggests association with specific pathways and presynaptical localizationXavier Miro
Department of Molecular Genetics, Instituto de Biologia Molecular de Barcelona, CID CSIC, E 08034 Barcelona, Spain
Synapse 45:259-69. 2002..Members of the PDE4 enzyme family are selectively inhibited by rolipram. Five different mRNA splice forms for PDE4D have been isolated...
- Phosphodiesterase regulation is critical for the differentiation and pattern of gene expression in granulosa cells of the ovarian follicleJy Young Park
Division of Reproductive Biology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305 5317, USA
Mol Endocrinol 17:1117-30. 2003..Here, we provide evidence that one of these feedback regulations involving the cyclic nucleotide phosphodiesterase PDE4D plays a critical role in cAMP signaling during the differentiation of granulosa cells of the ovarian follicle...
- RNA silencing identifies PDE4D5 as the functionally relevant cAMP phosphodiesterase interacting with beta arrestin to control the protein kinase A/AKAP79-mediated switching of the beta2-adrenergic receptor to activation of ERK in HEK293B2 cellsMartin J Lynch
Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, Wolfson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, United Kingdom
J Biol Chem 280:33178-89. 2005PDE4B and PDE4D provide >90% of PDE4 cAMP phosphodiesterase activity in human embryonic kidney (HEK293B2) cells...
- Genome-wide copy number analysis in esophageal adenocarcinoma using high-density single-nucleotide polymorphism arraysDerek J Nancarrow
Oncogenomics, Queensland Institute of Medical Research, Herston, Queensland, Australia
Cancer Res 68:4163-72. 2008..were also noted for known tumor suppressor genes (TSG), including CDKN2A, CDKN2B, SMAD4, and GALR1, and identified PDE4D and MGC48628 as potentially novel TSGs...
- Association between the PDE4D gene and ischaemic stroke in the Chinese Han populationYun Sun
Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China
Clin Sci (Lond) 117:265-72. 2009Recent findings suggests that PDE4D (gene encoding phosphodiesterase 4D) is a stroke-related gene in the Icelandic population, but it is still very controversial as to whether it is a susceptible gene for stroke in other populations...
- Oxidative stress employs phosphatidyl inositol 3-kinase and ERK signalling pathways to activate cAMP phosphodiesterase-4D3 (PDE4D3) through multi-site phosphorylation at Ser239 and Ser579Elaine V Hill
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
Cell Signal 18:2056-69. 2006..We identify a novel process through which reactive oxygen species activate long PDE4 isoforms so as to reduce cAMP levels and thereby promote inflammatory responses...
- Interaction between LIS1 and PDE4, and its role in cytoplasmic dynein functionHannah Murdoch
Molecular Pharmacology Group, Davidson Wolfson Link Bldgs, Institute of Neuroscience and Psychology, University of Glasgow, University Avenue, Glasgow G128QQ, UK
J Cell Sci 124:2253-66. 2011..This provides a further example to the growing notion that PDE4 itself may provide a signalling role independent of its catalytic activity, exemplified here by its modulation of dynein motor function...
- PKA-phosphorylation of PDE4D3 facilitates recruitment of the mAKAP signalling complexJennifer J Carlisle Michel
Howard Hughes Medical Institute and Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239 3098, USA
Biochem J 381:587-92. 2004..Our data suggest that activation of mAKAP-anchored PKA enhances the recruitment of PDE4D3, allowing for quicker signal termination...
- A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugsG Bolger
Cold Spring Harbor Laboratory, New York 11724
Mol Cell Biol 13:6558-71. 1993..Each of the four genes demonstrated a distinctive pattern of expression in RNA from human cell lines...
- Mdm2 directs the ubiquitination of beta-arrestin-sequestered cAMP phosphodiesterase-4D5Xiang Li
Neuroscience and Molecular Pharmacology, Wolfson and Davidson Buildings, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, United Kingdom
J Biol Chem 284:16170-82. 2009..for this is the ubiquitin-interacting motif located in the extreme C terminus of PDE4D5, which is specific to the PDE4D sub-family...
- Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERKXiang Li
Neuroscience and Molecular Pharmacology, Division of Integrative Biology, IBLS, Wolfson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
Biochem J 428:55-65. 2010..In the present paper, we report for the first time that PDE4 isoforms from the PDE4A and PDE4D subfamilies can be selectively modified by SUMO (small ubiquitin-related modifier)...
- Numerous distinct PKA-, or EPAC-based, signalling complexes allow selective phosphodiesterase 3 and phosphodiesterase 4 coordination of cell adhesionDaniel R Raymond
Department of Pharmacology and Toxicology, Queen s University, Kingston, ON, Canada K7L 3N6
Cell Signal 19:2507-18. 2007..PKA- or EPAC-containing complexes can contain either phosphodiesterase 3B, [PDE3B] or phosphodiesterase 4D [PDE4D], they do not contain both these phosphodiesterases...
- Characterization of five different proteins produced by alternatively spliced mRNAs from the human cAMP-specific phosphodiesterase PDE4D geneG B Bolger
Department of Veterans Affairs Medical Center, 151M, and Huntsman Cancer Institute, Department of Oncologic Sciences and Department of Medicine Hematology Oncology University of Utah Health Sciences Center, Salt Lake City, UT 84148, USA
Biochem J 328:539-48. 1997We have isolated and characterized complete cDNAs for two isoforms (HSPDE4D4 and HSPDE4A5) encoded by the human PDE4D gene, one of four genes that encode cAMP-specific rolipram-inhibited 3',5'-cyclic nucleotide phosphodiesterases (type ..
- The oligomerization state determines regulatory properties and inhibitor sensitivity of type 4 cAMP-specific phosphodiesterasesWito Richter
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305 5317, USA
J Biol Chem 279:30338-48. 2004..Taken together, our data indicate that dimerization defines the properties of PDE4 enzymes and suggest a common structural and functional organization for all PDEs...
- Heterozygous mutations in cyclic AMP phosphodiesterase-4D (PDE4D) and protein kinase A (PKA) provide new insights into the molecular pathology of acrodysostosisTadashi Kaname
Department of Medical Genetics, University of the Ryukyus Graduate School of Medicine, Okinawa, Japan
Cell Signal 26:2446-59. 2014..Recently, loss-of-function mutations in the gene encoding cAMP-hydrolyzing phosphodiesterase-4D (PDE4D) have been reported to cause this rare condition but the pathomechanism has not been fully elucidated...
- Mapping binding sites for the PDE4D5 cAMP-specific phosphodiesterase to the N- and C-domains of beta-arrestin using spot-immobilized peptide arraysGeorge S Baillie
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
Biochem J 404:71-80. 2007..We have identified a binding site in the beta-arrestin 2 N-domain for the common PDE4D catalytic unit and two regions in the beta-arrestin 2 C-domain that confer specificity for PDE4D5 binding...
- The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3 by phosphorylating it at Ser579R Hoffmann
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Davidson and Wolfson Buildings, IBLS, University of Glasgow, Glasgow G12 8QQ, UK
EMBO J 18:893-903. 1999..We identify a novel means of cross-talk between the cAMP and ERK signalling pathways whereby cell stimuli that lead to ERK2 activation may modulate cAMP signalling...
- Phosphorylation and activation of a cAMP-specific phosphodiesterase by the cAMP-dependent protein kinase. Involvement of serine 54 in the enzyme activationC Sette
Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University Medical Center, Stanford, California 94305 5317, USA
J Biol Chem 271:16526-34. 1996..These findings support the hypothesis that the PDE4D3 variant contains a regulatory domain target for phosphorylation at the amino terminus of the protein and that Ser54 in this domain plays a crucial role in activation...
- Crystal structure of phosphodiesterase 4D and inhibitor complex(1)Mi Eun Lee
Department of Chemistry, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong gu, Daejon 305 701, South Korea
FEBS Lett 530:53-8. 2002..The first crystal structure of PDE4D catalytic domain and a bound inhibitor, zardaverine, was determined...
- Cyclic AMP-dependent transcriptional up-regulation of phosphodiesterase 4D5 in human airway smooth muscle cells. Identification and characterization of a novel PDE4D5 promoterIvan R Le Jeune
Division of Therapeutics and Institute of Cell Signalling, University Hospital, Nottingham NG7 2UH, United Kingdom
J Biol Chem 277:35980-9. 2002Phosphodiesterase 4D (PDE4D), part of the complex cAMP-specific PDE4 family, plays a pivotal role in the regulation of airway smooth muscle relaxation by catalyzing the hydolysis of cAMP...
- Phosphodiesterase 4D (PDE4D) gene variants and the risk of ischemic stroke in a South Indian populationAnjana Munshi
Department of Molecular Biology, Institute of Genetics and Hospital for Genetic Diseases, Begumpet, Hyderabad 500016, India
J Neurol Sci 285:142-5. 2009..Many of the studies of PDE4D gene have focused on the original Icelandic findings but the association between specific SNPs and haplotypes has ..
- Meta-analysis of association between variation in the PDE4D gene and ischemic cerebral infarction risk in Asian populationsXiaowei Xu
Department of Neurology, First Affiliated Hospital, Sun Yat Sen University, Guangzhou, People s Republic of China
Neurogenetics 11:327-33. 2010Phosphodiesterase 4D (PDE4D) was found to be associated with increased risk of ischemic stroke by Iceland researchers in 2003. Replication studies have produced conflicting results...
- Many hypotheses but no replication for the association between PDE4D and strokeJonathan Rosand
Nat Genet 38:1091-2; author reply 1092-3. 2006
- mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling moduleK L Dodge
Howard Hughes Medical Institute and Vollum Institute, and Department of Pediatrics, Oregon Health Sciences University, Portland, OR 97201 3098, USA
EMBO J 20:1921-30. 2001..Disruption of PKA- mAKAP interaction prevents this enhancement of PDE4D3 activity, suggesting that the proximity of both enzymes in the mAKAP signaling complex forms a negative feedback loop to restore basal cAMP levels...
- Phosphodiesterase 4D forms a cAMP diffusion barrier at the apical membrane of the airway epitheliumAnthony P Barnes
Department of Cell and Developmental Biology and Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
J Biol Chem 280:7997-8003. 2005..Using reverse transcription-PCR, Western blotting, and activity measurements, PDE4D was identified as the major PDE species in airway epithelia...
- Variation in the PDE4D gene and ischemic stroke risk: a systematic review and meta-analysis on 5200 cases and 6600 controlsSteve Bevan
Centre for Clinical Neuroscience, St George s, University of London, Cranmer Terrace, Tooting, London, SW17 0RE, UK
Stroke 39:1966-71. 2008b>PDE4D was identified as the first novel gene associated with ischemic stroke risk. Replication studies have produced conflicting results, but many have been small and underpowered...
- The unique N-terminal domain of the cAMP phosphodiesterase PDE4D4 allows for interaction with specific SH3 domainsM B Beard
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, University of Glasgow, UK
FEBS Lett 460:173-7. 1999Of the five PDE4D isoenzymes, only the PDE4D4 cAMP specific phosphodiesterase was able to bind to SH3 domains...
- Evaluation of single nucleotide polymorphisms in the phosphodiesterase 4D gene (PDE4D) and their association with ischaemic stroke in a large German cohortG Kuhlenbaumer
Department of Neurology and Leibniz Institute for Atherosclerosis Research, University of Munster, Albert Schweitzer Str 33, 48129, Munster, Germany
J Neurol Neurosurg Psychiatry 77:521-4. 2006..which has been mapped to chromosome 5q12 in Icelandic families), has identified the phosphodiesterase 4D gene (PDE4D) gene as a good candidate gene...
- The gene encoding phosphodiesterase 4D confers risk of ischemic strokeSolveig Gretarsdottir
deCODE Genetics, Sturlugata 8, IS 101 Reykjavik, Iceland
Nat Genet 35:131-8. 2003..We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atherosclerosis...
- Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine suggest a conformation determinant of inhibitor selectivityQing Huai
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599 7260, USA
J Biol Chem 279:13095-101. 2004..IBMX binds to a subpocket that comprises key residues Ile-336, Phe-340, Gln-369, and Phe-372 of PDE4D2 or Val-782, Phe-786, Gln-817, and Phe-820 of PDE5A1. This subpocket may be a common site for binding nonselective inhibitors of PDEs...
- The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathwaysKimberly L Dodge-Kafka
Howard Hughes Medical Institute, Oregon Health and Sciences University, Portland, Oregon 97239, USA
Nature 437:574-8. 2005..Thus, two coupled cAMP-dependent feedback loops are coordinated within the context of the mAKAP complex, suggesting that local control of cAMP signalling by AKAP proteins is more intricate than previously appreciated...
- A major functional role for phosphodiesterase 4D5 in human airway smooth muscle cellsCharlotte K Billington
Division of Therapeutics and Molecular Medicine, University of Nottingham, Queens Medical Centre, Nottingham, UK
Am J Respir Cell Mol Biol 38:1-7. 2008..previously reported that PDE4 family members are likely to be important in this process, and that expression of PDE4D variants is actively regulated at the transcriptional level...
- beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to GiGeorge S Baillie
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute for Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom
Proc Natl Acad Sci U S A 100:940-5. 2003..are treated with the selective PDE4-inhibitor rolipram or when they are transfected with a catalytically inactive PDE4D mutant (PDE4D5-D556A) that competitively inhibits isoprenaline-stimulated recruitment of native PDE4 to the beta(2)..
- Compartmentalization of cAMP-dependent signaling by phosphodiesterase-4D is involved in the regulation of vasopressin-mediated water reabsorption in renal principal cellsEduard Stefan
Leibniz Institut fur Molekulare Pharmakologie, Berlin, Germany
J Am Soc Nephrol 18:199-212. 2007..PKA and cAMP-specific phosphodiesterase-4D (PDE4D) are located on AQP2-bearing vesicles...
- Lack of association between variations of PDE4D and ischemic stroke in the Japanese populationTomonaga Matsushita
Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa, Japan
Stroke 40:1245-51. 2009After the first genomewide association study of ischemic stroke identified PDE4D as a susceptible gene, many replication studies have been conducted...
- PGE(1) stimulation of HEK293 cells generates multiple contiguous domains with different [cAMP]: role of compartmentalized phosphodiesterasesAnna Terrin
Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padova, Italy
J Cell Biol 175:441-51. 2006..and genetic manipulation of phosphodiesterases (PDEs), we demonstrate that compartmentalized PDE4B and PDE4D are responsible for selectively modulating the concentration of cAMP in individual subcellular compartments...
- Genome-wide association analysis identifies PDE4D as an asthma-susceptibility geneBlanca E Himes
Harvard MIT Division of Health Sciences and Technology, Cambridge, MA, 02138, USA
Am J Hum Genet 84:581-93. 2009..The strongest region of association seen was on chromosome 5q12 in PDE4D. The phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila) gene (PDE4D) is a ..
- An anchored PKA and PDE4 complex regulates subplasmalemmal cAMP dynamicsDebbie Willoughby
Department of Pharmacology, University of Cambridge, Cambridge, UK
EMBO J 25:2051-61. 2006..Co-immunoprecipitation confirmed that gravin maintains a signaling complex that includes PKA and PDE4D. We propose that gravin-associated PDE4D isoforms provide a means to rapidly terminate subplasmalemmal cAMP ..
- Association of phosphodiesterase 4D gene polymorphisms with chronic obstructive pulmonary disease: relationship to interleukin 13 gene polymorphismShinsuke Homma
Department of Pulmonary Medicine, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences and University Hospital, University of Tsukuba, Tsukuba, Ibaraki 305 8575, Japan
Int J Mol Med 18:933-9. 2006..We hypothesized that polymorphisms of the phosphodiesterase 4D (PDE4D) gene activate its protein function which leads to the downregulation of cAMP, resulting in the development of ..
- Stroke genetics--focus on PDE4D geneAnjana Munshi
Department of Molecular Biology, Institute of Genetics and Hospital for Genetic Diseases, Begumpet, Hyderabad, India
Int J Stroke 3:188-92. 2008..Recently, the deCODE group has suggested an association between the phosphodiesterase 4D (PDE4D) gene and the risk of stroke in Icelanders...
- cAMP-specific phosphodiesterase HSPDE4D3 mutants which mimic activation and changes in rolipram inhibition triggered by protein kinase A phosphorylation of Ser-54: generation of a molecular modelR Hoffmann
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Davidson and Wolfson Buildings, IBLS, University of Glasgow, Glasgow G12 8QQ, Scotland, U K
Biochem J 333:139-49. 1998..The increase in susceptibility to inhibition by rolipram upon PKA-mediated phosphorylation is suggested to involve the disruption of a hydrogen-bond involving the side-chain hydroxy group of Ser-54...
- Phosphodiesterase 4D gene, ischemic stroke, and asymptomatic carotid atherosclerosisS Bevan
Department of Clinical Neuroscience, St George s Hospital Medical School, Tooting, London, UK
Stroke 36:949-53. 2005Phosphodiesterase 4D (PDE4D) was identified recently as the first novel stroke gene to predispose to ischemic stroke independently of conventional risk factors...
- Association of phosphodiesterase 4D gene with ischemic stroke in a Pakistani populationDanish Saleheen
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan
Stroke 36:2275-7. 2005Identification of STRK1 locus by the deCODE group followed by the discovery of phosphodiesterase 4D (PDE4D) gene in strong association with ischemic stroke patients has provided useful insights toward understanding the genetic etiology ..
- Association of PDE4D and IL-1 gene polymorphism with ischemic stroke in a Han Chinese populationNan Li
Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China
Brain Res Bull 81:38-42. 2010The single-nucleotide polymorphisms (SNPs) of the phosphodiesterase 4D (PDE4D) and interleukin-1 (IL-1) genes are associated with increased risk for the development of ischemic stroke (IS) in whites...
- Phosphodiesterase 4D and 5-lipoxygenase activating protein in ischemic strokeJames F Meschia
Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA
Ann Neurol 58:351-61. 2005..Iceland identified risk polymorphisms in two putative candidate genes for ischemic stroke: phosphodiesterase 4D (PDE4D) and 5-lipoxygenase activating protein (ALOX5AP)...
- Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women StudyQing Song
Morehouse School of Medicine, Atlanta, GA 30314, USA
Hum Mol Genet 15:2468-78. 2006An association between polymorphisms within the phosphodiesterase 4D gene (PDE4D) and ischemic stroke was initially reported in older adults from Iceland and has been supported by studies in several other primarily elderly populations...
- Association between phosphodiesterase 4D gene and ischaemic strokeJ M Staton
Department of Haematology, Royal Perth Hospital, Perth, Western Australia, Australia
J Neurol Neurosurg Psychiatry 77:1067-9. 2006An association between the phosphodiesterase 4D (PDE4D) gene and risk of ischaemic stroke in an Icelandic population has been suggested by the deCODE group.
- Polymorphisms of the phosphodiesterase 4D, cAMP-specific (PDE4D) gene and risk of ischemic stroke: a prospective, nested case-control evaluationRobert Y L Zee
Laboratory of Genetic and Molecular Epidemiology, Center for Cardiovascular Disease Prevention, Brigham and Women s Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, Massachusetts 02215, USA
Stroke 37:2012-7. 2006In an Icelandic population, gene variants of the phosphodiesterase 4D, cAMP-specific (PDE4D) gene were reported to be risk predictors for ischemic stroke...
- Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestinsStephen J Perry
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Science 298:834-6. 2002....
- The unique amino-terminal region of the PDE4D5 cAMP phosphodiesterase isoform confers preferential interaction with beta-arrestinsGraeme B Bolger
University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama 35294 3300, USA
J Biol Chem 278:49230-8. 2003Isoproterenol challenge of Hek-B2 cells causes a transient recruitment of the endogenous PDE4D isoforms found in these cells, namely PDE4D3 and PDE4D5, to the membrane fraction...
- ERK2 mitogen-activated protein kinase binding, phosphorylation, and regulation of the PDE4D cAMP-specific phosphodiesterases. The involvement of COOH-terminal docking sites and NH2-terminal UCR regionsS J Mackenzie
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Davidson Bldg, IBLS, University of Glasgow, Glasgow G12 8QQ, Scotland, United Kingdom
J Biol Chem 275:16609-17. 2000..isoforms, are proposed to amplify the small, inherent inhibitory effect that ERK2 phosphorylation exerts on the PDE4D catalytic unit...
- A whole genome association study of neuroticism using DNA poolingS Shifman
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Mol Psychiatry 13:302-12. 2008..We were able to replicate association of one SNP within the PDE4D gene in a second sample collected by our laboratory and in a family-based test in an independent sample; however, ..
- 1H NMR structural and functional characterisation of a cAMP-specific phosphodiesterase-4D5 (PDE4D5) N-terminal region peptide that disrupts PDE4D5 interaction with the signalling scaffold proteins, beta-arrestin and RACK1K John Smith
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, PO Box 363, B15 2TT, UK
Cell Signal 19:2612-24. 2007....
- Genetics of common polygenic strokeAnna F Dominiczak
Nat Genet 35:116-7. 2003
- Scanning peptide array analyses identify overlapping binding sites for the signalling scaffold proteins, beta-arrestin and RACK1, in cAMP-specific phosphodiesterase PDE4D5Graeme B Bolger
Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294 3300, USA
Biochem J 398:23-36. 2006..Modelled on the PDE4D catalytic domain, these form distinct well-defined surface-exposed patches on helices-15-16, for RACK1, and helix-..
- ALOX5AP gene and the PDE4D gene in a central European population of stroke patientsElin Lõhmussaar
Institutes of Human Genetics, GSF National Research Institute for Environment and Health, Neuherberg, Germany
Stroke 36:731-6. 2005Recent evidence has implicated the genes for 5-lipoxygenase activating protein (ALOX5AP) and phosphodiesterase 4D (PDE4D) as susceptibility genes for stroke in the Icelandic population...
- Phosphodiesterase 4D gene and risk of noncardiogenic ischemic stroke in a Korean populationMyeong Kyu Kim
Department of Neurology, Chonnam National University Medical School and Research Institute of Medical Science, Gwangju, Korea
J Korean Med Sci 24:307-10. 2009..different populations provide apparently conflicting evidence on the association between the phosphodiesterase 4D (PDE4D) gene and ischemic stroke...
- Association of phosphodiesterase 4D polymorphisms with ischemic stroke in a US population stratified by hypertension statusVictoria H Brophy
Roche Molecular Systems, Alameda, CA 94501, USA
Stroke 37:1385-90. 2006Phosphodiesterase 4D (PDE4D) underlies the STRK1 linkage peak for stroke on chromosome 5q12 identified in Iceland...
- Linkage of ischemic stroke to the PDE4D region on 5q in a Swedish populationSofie Nilsson-Ardnor
Department of Medical Biosciences, Umea University, SE 901 87, Umea, Sweden
Stroke 36:1666-71. 2005..demonstrated linkage for common forms of stroke to chromosome 5q12 and association between phosphodiesterase4D (PDE4D) and ischemic stroke...
- Phosphodiesterase 4D gene polymorphism is associated with ischaemic and haemorrhagic strokeHao Xue
Department of Cardiology, Chinese People s Liberation Army General Hospital, Beijing, PR China
Clin Sci (Lond) 116:335-40. 2009It has been reported that the variants of the PDE4D (phosphodiesterase 4D) gene are associated with stroke, especially with the combination of cardio-embolic and carotid stroke in the Icelandic population, but it is still very ..
- Familial aggregation, the PDE4D gene, and ischemic stroke in a genetically isolated populationM J E van Rijn
Department of Epidemiology and Biostatistics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands
Neurology 65:1203-9. 2005The purpose of this investigation was to study the familial aggregation of ischemic stroke and the association between the PDE4D gene and ischemic stroke.
- Genotype and haplotype association study of the STRK1 region on 5q12 among Japanese: a case-control studyTomohiro Nakayama
Division of Receptor Biology, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo 173 8610, Japan
Stroke 37:69-76. 2006..Gretarsdottir et al identified a candidate locus (STRK1) for cerebral infarction with a significant logarithm of odds score at 5q12 in whites in 2002 and subsequently ..
- The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoformS J Yarwood
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biology and Life Sciences, University of Glasgow, Davidson Building, Glasgow G12 8QQ, Scotland, United Kingdom
J Biol Chem 274:14909-17. 1999..RACK1 did not interact with other PDE4D isoforms or with known PDE4A, PDE4B, and PDE4C isoforms...
- Ischaemic stroke in hypertensive patients is associated with variations in the PDE4D genome regionHåkan Lövkvist
Department of Clinical Sciences, Lund, Neurology, Lund University Hospital, Lund, Sweden
Eur J Hum Genet 16:1117-25. 2008Previous Icelandic studies reported that single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) region and the 5-lipoxygenase activating protein ALOX5AP were associated with ischaemic stroke, whereas other studies ..
- Three-dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivityQing Huai
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA
Structure 11:865-73. 2003..Docking of the PDE5 inhibitor sildenafil into the PDE4 catalytic pocket further helps understand inhibitor selectivity...
- Association of phosphodiesterase 4D gene G0 haplotype and ischaemic stroke in a Greek populationL Fidani
Department of General Biology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
Eur J Neurol 14:745-9. 2007We have examined the association of phosphodiesterase 4D (PDE4D) single nucleotide polymorphism (SNP45) and microsatellite marker AC008818-1 with ischaemic stroke, in an independent cohort of Greek patients and control individuals with ..
- PDE4D and ALOX5AP genetic variants and risk for Ischemic Cerebrovascular Disease in SwedenKonstantinos Kostulas
Department of Neurology, Neuro Angiological Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, S 141 86 Huddinge, Sweden
J Neurol Sci 263:113-7. 2007Genetic variants in Phosphodiesterase 4D (PDE4D) and 5-lipoxygenase activating protein (ALOX5AP) have been shown to confer risk of Ischemic Cerebrovascular Disease (ICVD) in Iceland...
- Delineation of RAID1, the RACK1 interaction domain located within the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5Graeme B Bolger
Veterans Affairs Medical Center, Huntsman Cancer Institute, Division of Oncology, Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, UT 84148, USA
BMC Biochem 3:24. 2002..Two-hybrid analysis of truncation and mutant constructs of the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5 were used to define a domain conferring interaction with the signaling scaffold protein, RACK1...
- Association of Phosphodiesterase 4D with ischemic stroke: a population-based case-control studyDaniel Woo
Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH 45267 0525, USA
Stroke 37:371-6. 2006The Phosphodiesterase 4D (PDE4D) gene was reported recently to be associated with ischemic stroke in an Icelandic population. The association was found predominately with large vessel and cardioembolic stroke...
- cAMP-specific phosphodiesterase-4D5 (PDE4D5) provides a paradigm for understanding the unique non-redundant roles that PDE4 isoforms play in shaping compartmentalized cAMP cell signallingM J Lynch
Division of Biochemistry and Molecular Biology, IBLS Institute of Biomedical and Life Sciences, Wolfson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, U K
Biochem Soc Trans 35:938-41. 2007....
- Phosphodiesterase 4D and 5-lipoxygenase activating protein genes and risk of ischemic stroke in SardiniansGiovanni Quarta
Department of Cardiology, University La Sapienza, Ospedale Sant Andrea, Rome
Eur J Hum Genet 17:1448-53. 2009Genetic factors contribute to the risk of ischemic stroke (IS). The phosphodiesterase-4D (PDE4D) and the 5-lipoxygenase activating protein (ALOX5AP) genes were identified as contributors to stroke in an Icelandic population...
- Localization of a susceptibility gene for common forms of stroke to 5q12Solveig Gretarsdottir
deCODE Genetics, Reykjavik, Iceland
Am J Hum Genet 70:593-603. 2002..This locus on 5q12, which we have designated as "STRK1," does not correspond to known susceptibility loci for stroke or for its risk factors and represents the first ..
- Identification of a surface on the beta-propeller protein RACK1 that interacts with the cAMP-specific phosphodiesterase PDE4D5M R Steele
Veterans Affairs Medical Center, Huntsman Cancer Institute, Department of Medicine Division of Oncology and Oncological Science, University of Utah Health Sciences Center, 500 Foothill Drive, Salt Lake City, UT 84148, USA
Cell Signal 13:507-13. 2001..We propose that this surface of RACK1 is the major site for its interaction with the unique amino-terminal region of PDE4D5...
- PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteriesAntónio José Santos-Silva
Centro de Investigacao em Ciencias da Saude, Universidade da Beira Interior, Av Infante D Henrique, 6200 506 Covilha, Portugal
Eur J Pharmacol 582:102-9. 2008..in human umbilical artery smooth muscle was analysed by RT-PCR and the expression of PDE1B, PDE3A, PDE3B, PDE4C, PDE4D and PDE5A was detected...
- Genome-wide catalogue of chromosomal aberrations in barrett's esophagus and esophageal adenocarcinoma: a high-density single nucleotide polymorphism array analysisJian Gu
Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Unit 1340, 1155 Pressler Boulevard, Houston, TX 77030, USA
Cancer Prev Res (Phila) 3:1176-86. 2010..recurrent small regions of chromosomal loss disrupted single genes, including FHIT, WWOX, RUNX1, KIF26B, MGC48628, PDE4D, C20orf133, GMDS, DMD, and PARK2, most of which are common fragile site regions in the human genome...
- Both protein kinase A and exchange protein activated by cAMP coordinate adhesion of human vascular endothelial cellsStuart J Netherton
Department of Pharmacology and Toxicology, Queen s University, Kingston, ON, Canada, K7L 3N6
Circ Res 101:768-76. 2007..complexes in both macro- and micro-VECs and demonstrate that each of these complexes contains either PDE3B or PDE4D but not both of these PDEs...
- Cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase is functional in bovine mammary glandV Dostaler-Touchette
Centre de Recherche en Biologie de la Reproduction, Departement des Sciences Animales, Universite Laval, Quebec, Canada
J Dairy Sci 92:3757-65. 2009..Reverse transcription PCR revealed that the PDE4D transcript was amplified, and the expected size fragment was obtained in a 1% agarose gel...
- Cilomilast: a second generation phosphodiesterase 4 inhibitor for asthma and chronic obstructive pulmonary diseaseM A Giembycz
Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK
Expert Opin Investig Drugs 10:1361-79. 2001..or PDE4, isoenzyme that predominates in pro-inflammatory and immune cells and is ten-fold more selective for PDE4D than for PDE4A, B and C...
- Long-term hormonal regulation of the cAMP-specific phosphodiesterases in cultured FRTL-5 thyroid cellsS I Takahashi
Department of Pediatrics, University of North Carolina at Chapel Hill, 27599, USA
Biochim Biophys Acta 1540:68-81. 2001..Under basal conditions, transcripts corresponding to PDE4A, PDE4B, PDE4C, and PDE4D were present...
- Expression of the cAMP-phosphodiesterase PDE4D isoforms and age-related changes in follicle-stimulating hormone-stimulated PDE4 activities in immature rat sertoli cellsGuénaëlle Levallet
EA 2608, INRA USC 2006, Laboratoire Oestrogènes et Reproduction, Universite de Caen, 14032 Caen, France
Biol Reprod 76:794-803. 2007..RT-PCR and immunoblotting experiments showed that almost all the PDE4D isoforms, known as the main cAMP-regulated rolipram-sensitive PDE in Sertoli cells, were expressed throughout the ..
- Vascular smooth muscle cell phosphodiesterase (PDE) 3 and PDE4 activities and levels are regulated by cyclic AMP in vivoDouglas G Tilley
Department of Pharmacology and Toxicology, Queen s University, Kingston, Ontario, Canada
Mol Pharmacol 62:497-506. 2002..agent induced increase in PDE3 and PDE4, 1) systemic administration of forskolin increased PDE3A, PDE3B, and PDE4D mRNA levels in aortic VSMC and femoral artery VSMC, 2) local delivery of dbcAMP increased PDE3A, PDE3B, and PDE4D3 ..
- Phosphodiesterase 4 inhibition synergizes with relaxin signaling to promote decidualization of human endometrial stromal cellsOlaf Bartsch
Institute for Hormone and Fertility Research, University of Hamburg, 20251 Hamburg, Germany
J Clin Endocrinol Metab 89:324-34. 2004..Gene expression for PDE4D and PDE4C was significantly up-regulated during in vitro decidualization...
- Characterization of novel phosphodiesterases in the bovine ovarian follicleMaxime Sasseville
Departement des Sciences Animales, Centre de Recherche en Biologie de la Reproduction, Universite Laval, Sainte Foy, Quebec, Canada
Biol Reprod 81:415-25. 2009..rodents, the current mammalian model of PDE distribution in the ovarian follicle predicts Pde3a in the oocyte and Pde4d in the somatic cells...
- Selective activation of rolipram-sensitive, cAMP-specific phosphodiesterase isoforms by phosphatidic acidG Nemoz
Unité 352 Institut National de la Santé de de la Recherche Médicale, Biochimie et Pharmacologie Institut National des Sciences Appliquées Lyon, Villeurbanne, France
Mol Pharmacol 51:242-9. 1997..activation by using recombinant cAMP-specific PDE4 isoforms derived from three different genes (PDE4A, PDE4B, and PDE4D)...
- Regulation of 3',5'-cAMP in preglomerular smooth muscle and endothelial cells from genetically hypertensive ratsDongmei Cheng
University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
Hypertension 56:1096-101. 2010..both cell types from both rat strains, mRNA levels for the PDE4B subtype exceeded levels for the PDE4A, PDE4C, and PDE4D subtypes, and small interfering RNA knockdown of PDE4B mRNA in SHR smooth muscle cells increased isoproterenol-..
- Cyclic AMP phosphodiesterases are localized in regions of the mouse brain associated with reinforcement, movement, and affectJ A Cherry
Department of Psychology, Boston University, Massachusetts 02215, USA
J Comp Neurol 407:287-301. 1999..specific antibodies were generated against the proteins encoded by each of three dunce homologs PDE4A, PDE4B, and PDE4D in the mouse. On Western blots, these antibodies recognized multiple protein species in all brain regions studied...
- Deletion of phosphodiesterase 4D in mice shortens alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesisAnnette Robichaud
Merck Frosst Centre for Therapeutic Research, Pointe Claire Dorval, Quebec, Canada
J Clin Invest 110:1045-52. 2002..The specific roles of PDE4B and PDE4D in this model were studied using mice deficient in either subtype...
- Phosphodiesterase type 4 isozymes expression in human brain examined by in situ hybridization histochemistry and[3H]rolipram binding autoradiography. Comparison with monkey and rat brainS Pérez-Torres
Department of Neurochemistry, Instituto de Investigaciones Biomédicas de Barcelona, CSIC IDIBAPS, C Rosselló 161, 6a, E 08036, Barcelona, Spain
J Chem Neuroanat 20:349-74. 2000..examined the distribution of four different cyclic AMP-specific phosphodiesterase isozyme (PDE4A, PDE4B, PDE4C and PDE4D) mRNAs in the brain of different species by in situ hybridization histochemistry and by autoradiography with [3H]..
- Antidepressant-like profile and reduced sensitivity to rolipram in mice deficient in the PDE4D phosphodiesterase enzymeHan Ting Zhang
Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Neuropsychopharmacology 27:587-95. 2002..In the present study, immunoblot analysis showed loss of phosphodiesterase 4D (PDE4D) expression in the cerebral cortex and hippocampus of PDE4D knockout (PDE4D-/-) mice, but unchanged PDE4A and ..
- Carbon-11 labeled papaverine as a PET tracer for imaging PDE10A: radiosynthesis, in vitro and in vivo evaluationZhude Tu
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA
Nucl Med Biol 37:509-16. 2010..inhibitor of phosphodiesterase (PDE) 10A with IC(50) values of 36 nM for PDE10A, 1,300 nM for PDE3A and 320 nM for PDE4D, has served as a useful pharmaceutical tool to study the physiological role of PDE10A...
- The role of the PDE4D cAMP phosphodiesterase in the regulation of glucagon-like peptide-1 releaseW K Ong
Strathclyde Institute of Pharmacy, Cell Biology Group, University of Strathclyde, Glasgow, UK
Br J Pharmacol 157:633-44. 2009..As cAMP is hydrolysed by cAMP phosphodiesterases (PDEs), we determined the role of PDEs and particularly PDE4 in regulating GLP-1 release...
- Evolutionarily conserved role of calcineurin in phosphodegron-dependent degradation of phosphodiesterase 4DHong Zhu
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA
Mol Cell Biol 30:4379-90. 2010..calcineurin binds directly to and inhibits the proteosomal degradation of cAMP-hydrolyzing phosphodiesterase 4D (PDE4D)...
- Subtype selectivity in phosphodiesterase 4 (PDE4): a bottleneck in rational drug designP Srivani
Molecular Modeling Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India
Curr Pharm Des 14:3854-72. 2008..followed by a detailed structural analysis of more than three dozen available X-ray structures of PDE4B and PDE4D. Usually, the lack of a 3-dimensional structure of a target protein is a bottleneck for rational drug design ..
- Stimulatory phosphorylation of cAMP-specific PDE4D5 by contractile agonists is mediated by PKC-dependent inactivation of protein phosphatase 2AKarnam S Murthy
Department of Physiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA
Am J Physiol Gastrointest Liver Physiol 294:G327-35. 2008..by PKA-mediated phosphorylation of cAMP-specific phosphodiesterase 3A (PDE3A) and PDE4D5; the latter is the only PDE4D isoform expressed in smooth muscle...
- Behavioral and neurochemical characterization of mice deficient in the phosphodiesterase-4B (PDE4B) enzymeJudith A Siuciak
CNS Discovery Research, Pfizer Global Research and Development, Groton, CT, 06340, USA
Psychopharmacology (Berl) 197:115-26. 2008..Four separate PDE4 genes (PDE4A, PDE4B, PDE4C, and PDE4D) have been identified...
- Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2M Sullivan
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, IBLS, Davidson and Wolfson Buildings, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
Biochem J 333:693-703. 1998..produce this short PDE4A isoform shown to occur at a different position from that seen in both the rat PDE4B and PDE4D genes...
- Phosphodiesterase-4 influences the PKA phosphorylation status and membrane translocation of G-protein receptor kinase 2 (GRK2) in HEK-293beta2 cells and cardiac myocytesXiang Li
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, IBLS, Wolfson Link Building, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, UK
Biochem J 394:427-35. 2006..inactivated, either chemically with rolipram or by siRNA (small interfering RNA)-mediated knockdown of PDE4B and PDE4D. PDE4-selective inhibition by rolipram facilitates the isoprenaline-induced membrane translocation of GRK2, ..
- The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4DF Mori
Department of Neurochemistry and Neuropharmacology, Institut d Investigacions Biomediques de Barcelona, CSIC IDIBAPS, CIBERNED, Rossello 161, 6 a 08036 Barcelona, Spain
J Chem Neuroanat 40:36-42. 2010..distribution and cellular localization of the four gene transcripts of the PDE4 subfamily (PDE4A, PDE4B, PDE4C and PDE4D) in human brainstem...
- Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon-based somatic mutagenesis screenEric P Rahrmann
Department of Genetics, Cell Biology, and Development and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
Cancer Res 69:4388-97. 2009..analysis of transposon insertions identified candidate prostate cancer genes at common insertion sites, including Pde4d. PDE4D was also overexpressed in human prostate cancer patient samples and cell lines, and changes in PDE4D mRNA ..
- Anxiogenic-like behavioral phenotype of mice deficient in phosphodiesterase 4B (PDE4B)Han Ting Zhang
Department of Behavioral Medicine and Psychiatry, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA
Neuropsychopharmacology 33:1611-23. 2008..However, the functions of the four PDE4 subfamilies (PDE4A, PDE4B, PDE4C, and PDE4D) remain largely unknown...
- Palladium-catalyzed cross-coupling reactions for the synthesis of 6, 8-disubstituted 1,7-naphthyridines: a novel class of potent and selective phosphodiesterase type 4D inhibitorsR Hersperger
Novartis Pharma AG, Research, CH 4002 Basel, Switzerland
J Med Chem 43:675-82. 2000..synthesis of 6,8-disubstituted 1,7-naphthyridines and their characterization as potent and selective inhibitors of PDE4D which suppress the oxidative burst in human eosinophils with IC(50) values as low as 0.7 nM...
- HORMONAL REGULATION OF PHOSPHODIESTERASESMarco Conti; Fiscal Year: 2006..In the first Specific Aim, the biochemical changes that induce impaired ovulation and follicle function in the PDE4D null mice will be studied using granulosa cell cultures...
- Phosphodiesterease-4 (PDE4) as a Novel Target to Reduce Ethanol ConsumptionHan Ting Zhang; Fiscal Year: 2012..in the regulation of ethanol consumption using the two-bottle choice test in mice deficient in PDE4A, PDE4B, or PDE4D. Successfully completion of these experiments will not only establish the role of PDE4 in the regulation of ..
- Hormonal Regulation of PhosphodiestrasesMarco Conti; Fiscal Year: 2012..Indeed, our analysis of PDE4 KO phenotypes has provided initial evidence that PDE4D and PDE4B play distinct functions in the body...
- Calcineurin Phosphatase in Cell Signaling PathwaysChi Wing Chow; Fiscal Year: 2010..The specific aims of this proposal are to examine: 1) The role of CnA-beta in the expression of PDE4D;and 2) The role of CnA-beta in the phosphorylation-dependent protein degradation...
- Gene silencing of phosphodiesterase-4D (PDE4D) as a therapeutic approach to beta Han Ting Zhang; Fiscal Year: 2009..data from our laboratory and others, we hypothesize that, among the four PDE4 subtypes (PDE4-A, B, C, and D), PDE4D plays a major role in the mediation of memory loss associated with AD...
- Spatiotemporal regulation of beta adrenoceptor signaling in cardiacmyocytesYang K Xiang; Fiscal Year: 2013..Aim 1. To characterize the effects of subtype-specific bAR/PDE4D complexes on spatiotemporal cAMP/PKA signaling propagation in cardiac myocytes...
- Phosphodiesterase 4 Subtype Selective Modulators for Psychiatric DiseaseMark E Gurney; Fiscal Year: 2012..We recently described the discovery of isoform-selective, allosteric modulators of PDE4D that bind to a high affinity site on an N-terminal regulatory domain known as Upstream Conserved Region 2 (UCR2)...
- The MITF transcriptional network: melanoma risk and carcinogenesisDavid E Fisher; Fiscal Year: 2013..Aim 2 investigates a putative melanoma oncogene, PDE4D-IP, amplified in 25% of melanomas, and predicted to disrupt cAMP homeostasis, thereby producing a novel oncogenic ..
- Mechanisms of Sleepiness Symptoms in Sleep Apnea and Cardiovascular DiseaseVictoria M Pak; Fiscal Year: 2013..different frequency of polymorphisms in genes such as NOX-2, NOX p22phox, tumor necrosis factor-alpha (TNF-?), and PDE4D, will modify the degree of sleepiness symptoms in individuals with similar degrees of sleep-disordered breathing...
- Development of a Novel Cell Based PDE10A Assay for Antipsychotic Drug DiscoveryWenshan Hao; Fiscal Year: 2012..1. Generate stable HEK293-CNG-TSHR-PDE10A cell line. 2. Knock out PDE4D and PDE4B genes to generate HEK293-CNG-TSHR-PDE10A-PDE4D-/--PDE4B-/- cell line (PDE10A cell line). 3...
- Novel prostate cancer oncogenes identified by transposon mutagenesisPaul C Marker; Fiscal Year: 2013..One of the first genes identified in the mouse screen, PDE4D, was also over-expressed in human prostate cancer patient samples...
- TRPV1 regulation by B-arrestinsELAINE DARCEY POR; Fiscal Year: 2012..TRPV1 desensitization, additional experiments were conducted which confirmed association of the phosphodiesterase PDE4D with Beta-arrestin in TG neurons...
- Canthinones as Human Isozyme Selective PDE4 InhibitorsKEVIN CZERWINSKI; Fiscal Year: 2002..In addition, the human isozymes of PDE4 (PDE4A, PDE4C, PDE4D) are highly homologous to PDE4B...
- NEUROPSYCHOPHARMACOLOGY OF CYCLIC AMP PDE INHIBITORSJAMES O DONNELL; Fiscal Year: 2007..do so will require a better understanding of the roles of the PDE4 subtypes expressed in brain (PDE4A, PDE4B, and PDE4D) in mediating the behavioral effects of PDE4 inhibitors...
- PDE4D Allosteric Modulators for Treating Cognitive ImpairmentMark E Gurney; Fiscal Year: 2013..We are seeking to develop a new treatment for AD based on allosteric modulation of phosphodiesterase 4D (PDE4D). Ideally, the treatment will reverse or stabilize cognitive decline due to AD.
- SALIVARY SECRETION-ROLE OF CALCIUMEILEEN WATSON; Fiscal Year: 2005..of PDE4 isoenzymes which will be identified by immunoprecipitation and immunoblot analysis with specific PDE4D antibodies, and PDE assays, and amylase release...
- MINORITY PREDOCTORAL FELLOWSHIP PROGRAMSusana Neves; Fiscal Year: 2005..This loop involves the differential expression of the cyclic nucleotide phosphodiesterase PDE4D long and short isoforms...
- Siblings With Ischemic Stroke Study (SWISS)JAMES MESCHIA; Fiscal Year: 2009..DNA banking and the creation of permanent lymphoblastoid cell lines will be done to permit future collaborative efforts to study the genetic basis for stroke risk. ..
- ISGS: The Ischemic Stroke Genetics StudyJAMES MESCHIA; Fiscal Year: 2006..The application and SWISS share the same definitions for the present and absence of phenotype and key enrollment criteria. ..
- Molecular Determinants of Coronary Artery DiseaseQing Wang; Fiscal Year: 2004..The accomplishment of research objectives in this proposal has the potential to have a substantial impact on the understanding of the molecular mechanism of CAD and MI, thereby facilitating better prevention, diagnosis and therapy. ..
- SEXUAL DIFFERENTIATION OF MOUSE VOMERONASAL FUNCTIONJames Cherry; Fiscal Year: 2004....
- Central betal adrenergic receptors and behaviorHan Ting Zhang; Fiscal Year: 2004..This will lead to the better understanding of pathophysiology and pharmacotherapy of depression. ..
- GENES FOR VASCULAR MORPHOGENESIS: A GENETIC APPROACHQing Wang; Fiscal Year: 2003..Moreover, understanding the genetic mechanisms underlying KTS offers possibilities for treatment of KTS as well as conditions such as cancer that depend on angiogenesis. ..
- Molecular Mechanisms of Cardiac ArrhythmiasQing Wang; Fiscal Year: 2005..These studies may provide a new framework for the rational design of therapeutic agents. ..
- REGULATION OF THE CAMP SPECIFIC PHOSPHODIESTERASESGraeme Bolger; Fiscal Year: 2003..5. The two-hybrid system will be used to clone cDNAs encoding proteins that interact with 4 novel PDE4 isoforms. ..
- TGF-BETA, CHLORIDE CHANNELS AND APOPTOSIS OF AIRWAY EPITHELIAL CELLSDevendra K Agrawal; Fiscal Year: 2010..Such investigations would provide unique insights to the pathophysiologic process of chronic asthma and the means to prevent or reverse the disease. ..
- mAKAP-orchestrated phosphorylation events: regulation of PDE4D3Kimberly L Dodge Kafka; Fiscal Year: 2010..This study will further our understanding of the molecular mechanism of cardiac hypertrophy and help to identify novel targets for drug design to aid in the treatment of hypertrophy. ..
- FLT3-LIGAND, IMMUNOMODULATION AND THERAPY IN ASTHMADEVENDRA AGRAWAL; Fiscal Year: 2008..The long-term goal of this study is to better define the potential mechanisms of action of FL to prevent and reverse allergic airway inflammation and associated changes in pulmonary function. ..
- Polymorphisms in Inflammation Genes and Bladder Cancer RiskJian Gu; Fiscal Year: 2008..The application will allow us to have a comprehensive picture of the effects of functional polymorphisms in inflammation related genes on BC risk. [unreadable] [unreadable] [unreadable]..
- Benzo[alpha]pyrene Diol Epoxide (BPDE) Sensitivity at 9*Jian Gu; Fiscal Year: 2005..The proposed susceptibility marker may be useful as biomarkers to identify high-risk populations that could then be targeted for intensive smoking-cessation programs and could be enrolled into chemoprevention trials. ..
- Familial Aggregation of StrokeDaniel Woo; Fiscal Year: 2005..Determining the component of the familial aggregation of ICH that is independent of the familial aggregation of environmental risk factors is a fundamental step in the analysis of the genetic epidemiology of stroke. ..
- CORTICOLIMBIC SYSTEM AND SCHIZOPHRENIAFrancine Benes; Fiscal Year: 2002....
- Genomewide search for modifiers of severity in beta-tha*Andreas Braun; Fiscal Year: 2004..To our knowledge, using 100,000 gene-based SNPs, this will be the largest genomewide association study ever undertaken in an attempt to identify disease susceptibility or protective alleles. ..