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1. Full Text The upstream conserved regions (UCRs) mediate homo-and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases (PDE4s)
by Xie, Moses and Blackman, Brigitte and Scheitrum, Colleen and Mika, Delphine and Blanchard, Elise and Lei, Tao and Conti, Marco and Richter, Wito
Biochemical Journal, ISSN 0264-6021, 1760, Volume 459, Issue 3, pp. 539 - 550
PDE4s (type 4 cyclic nucleotide phosphodiesterases) are divided into long and short forms by the presence or absence of conserved N-terminal domains termed... 
Dimer | Oligomerization | CAMP | Cyclic nucleotide phosphodiesterase 4 (PDE4) | Phosphodiesterase | DOMAIN | CAMP-SPECIFIC PHOSPHODIESTERASE | PROTEIN-KINASE | MAP KINASE | BIOCHEMISTRY & MOLECULAR BIOLOGY | dimer | GEL-FILTRATION | DENSITY GRADIENT CENTRIFUGATION | cyclic nucleotide phosphodiesterase 4 (PDE4) | ROD CGMP-PHOSPHODIESTERASE-6 | cAMP | CGMP-BINDING | oligomerization | PHOSPHATIDIC-ACID BINDING | phosphodiesterase | CATALYTIC SITE | Phosphorylation | Molecular Weight | Humans | Protein Multimerization | Cercopithecus aethiops | Isoenzymes - chemistry | Recombinant Fusion Proteins - metabolism | Cytosol - enzymology | Cyclic AMP-Dependent Protein Kinases - genetics | Isoenzymes - metabolism | HEK293 Cells | Conserved Sequence | Luminescent Proteins - chemistry | Protein Interaction Domains and Motifs | Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism | Cyclic Nucleotide Phosphodiesterases, Type 4 - chemistry | Dimerization | Cyclic AMP-Dependent Protein Kinases - metabolism | Recombinant Proteins - metabolism | Amino Acid Sequence | Isoenzymes - genetics | Rats | Recombinant Proteins - chemistry | Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics | Recombinant Fusion Proteins - chemistry | Animals | Cytosol - metabolism | Luminescent Proteins - genetics | Protein Processing, Post-Translational | Enzyme Activation | COS Cells | Luminescent Proteins - metabolism | PDE4
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2. Full Text Interaction between phosphodiesterases in the regulation of the cardiac β-adrenergic pathway
by Zhao, Claire Y and Greenstein, Joseph L and Winslow, Raimond L
Journal of Molecular and Cellular Cardiology, ISSN 0022-2828, 2015, Volume 88, pp. 29 - 38
Abstract In cardiac myocytes, the second messenger cAMP is synthesized within the β-adrenergic signaling pathway upon sympathetic activation. It activates... 
Cardiovascular | β-adrenergic pathway | Cyclic nucleotides | Computational model | Signaling networks | Cardiac myocytes | Phosphodiesterase | CARDIAC & CARDIOVASCULAR SYSTEMS | COMPUTATIONAL MODELS | HEART-FAILURE | beta-adrenergic pathway | CAMP EARLY REPRESSOR | CGMP PHOSPHODIESTERASES | PROTEIN-KINASES | FEEDBACK LOOP | CELL BIOLOGY | CARDIOMYOCYTE APOPTOSIS | NITRIC-OXIDE | CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE | RAT VENTRICULAR MYOCYTES | Cyclic Nucleotide Phosphodiesterases, Type 3 - genetics | Phosphorylation | Humans | Myocardial Contraction - physiology | Cyclic Nucleotide Phosphodiesterases, Type 2 - genetics | Cyclic AMP-Dependent Protein Kinases - genetics | Myocardium - metabolism | Cyclic Nucleotide Phosphodiesterases, Type 3 - metabolism | Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism | Binding Sites | Cyclic AMP - metabolism | Binding, Competitive | Cyclic AMP-Dependent Protein Kinases - metabolism | Myocytes, Cardiac - cytology | Signal Transduction | Models, Cardiovascular | Cyclic Nucleotide Phosphodiesterases, Type 2 - metabolism | Gene Expression Regulation | Cyclic Nucleotide Phosphodiesterases, Type 1 - metabolism | Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics | Feedback, Physiological | Animals | Cyclic GMP - metabolism | Myocytes, Cardiac - metabolism | Protein Binding | Mice | Cyclic Nucleotide Phosphodiesterases, Type 1 - genetics
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3. Full Text AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B
by Johanns, M and Lai, Y.-C and Hsu, M.-F and Jacobs, R and Vertommen, D and Van Sande, J and Dumont, J.E and Woods, A and Carling, D and Hue, L and Viollet, B and Foretz, M and Rider, M.H
Nature Communications, ISSN 2041-1723, 03/2016, Volume 7, Issue 1, p. 10856
Biguanides such as metformin have previously been shown to antagonize hepatic glucagon-stimulated cyclic AMP (cAMP) signalling independently of AMP-activated... 
GLYCOGEN-METABOLISM | SKELETAL-MUSCLE | CULTURED RAT HEPATOCYTES | HORMONAL-CONTROL | PROTEIN-KINASE | MULTIDISCIPLINARY SCIENCES | MULTISITE PHOSPHORYLATION | BINDING-PROTEIN | GENE-EXPRESSION | MASS-SPECTROMETRY | GLUCOSE-PRODUCTION | AMP-Activated Protein Kinases - metabolism | Phosphorylation | Signal Transduction | Mice, Inbred C57BL | Cells, Cultured | Enzyme Activators - metabolism | Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics | Hepatocytes - metabolism | Amino Acid Motifs | Mice, Knockout | Animals | Glucagon - metabolism | Mice | Enzyme Activation | Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism | Cyclic AMP - metabolism | Cyclic Nucleotide Phosphodiesterases, Type 4 - chemistry | AMP-Activated Protein Kinases - genetics | Hepatocytes - enzymology
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4. Full Text Phosphodiesterase isoform‐specific expression induced by traumatic brain injury
by Oliva, Anthony A and Kang, Yuan and Furones, Concepcion and Alonso, Ofelia F and Bruno, Olga and Dietrich, W. Dalton and Atkins, Coleen M
Journal of Neurochemistry, ISSN 0022-3042, 12/2012, Volume 123, Issue 6, pp. 1019 - 1029
Traumatic brain injury ( TBI ) results in significant inflammation which contributes to the evolving pathology. Previously, we have demonstrated that cyclic... 
traumatic brain injury | phosphodiesterase | cAMP | fluid‐percussion | inflammation | isoform | fluid-percussion | FUNCTIONAL RECOVERY | LOCALIZATION | DIFFERENTIAL EXPRESSION | BIOCHEMISTRY & MOLECULAR BIOLOGY | SPLICE VARIANTS | NEUROSCIENCES | PDE4 INHIBITORS | ROLIPRAM | RAT-BRAIN | TNF-ALPHA | CAMP-SPECIFIC PHOSPHODIESTERASES | Cyclic Nucleotide Phosphodiesterases, Type 3 - genetics | Phosphoric Diester Hydrolases - biosynthesis | Male | Cyclic Nucleotide Phosphodiesterases, Type 1 - biosynthesis | Cyclic Nucleotide Phosphodiesterases, Type 1 - antagonists & inhibitors | Phosphorylation - genetics | Cyclic Nucleotide Phosphodiesterases, Type 3 - metabolism | Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism | Cyclic Nucleotide Phosphodiesterases, Type 4 - biosynthesis | Disease Models, Animal | Phosphoric Diester Hydrolases - metabolism | Isoenzymes - genetics | Brain Injuries - enzymology | Rats | Phosphoric Diester Hydrolases - genetics | Brain Injuries - genetics | Brain Injuries - therapy | Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics | Rats, Sprague-Dawley | Cyclic Nucleotide Phosphodiesterases, Type 3 - biosynthesis | Cyclic AMP - antagonists & inhibitors | Animals | Cyclic AMP - biosynthesis | Gene Expression Regulation, Enzymologic - genetics | Isoenzymes - biosynthesis | Cyclic Nucleotide Phosphodiesterases, Type 1 - genetics | Isoenzymes - antagonists & inhibitors | Brain | Neurons | Analysis | Injuries | Neurochemistry | Enzymes | Brain damage | Gene expression | Trauma | Ca super(2+)/calmodulin-dependent phosphodiesterase | Phosphorylation | Traumatic brain injury | Cortex (parietal) | Cyclic AMP | Inflammation | Glia | Western blotting
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5. Full Text Phenotypic, chemical and functional characterization of cyclic nucleotide phosphodiesterase 4 (PDE4) as a potential anthelmintic drug target
by Long, Thavy and Rojo-Arreola, Liliana and Shi, Da and El-Sakkary, Nelly and Jarnagin, Kurt and Rock, Fernando and Meewan, Maliwan and Rascón, Alberto A and Lin, Lin and Cunningham, Katherine A and Lemieux, George A and Podust, Larissa and Abagyan, Ruben and Ashrafi, Kaveh and McKerrow, James H and Caffrey, Conor R
PLoS Neglected Tropical Diseases, ISSN 1935-2727, 07/2017, Volume 11, Issue 7, p. e0005680
Background Reliance on just one drug to treat the prevalent tropical disease, schistosomiasis, spurs the search for new drugs and drug targets. Inhibitors of... 
CAENORHABDITIS-ELEGANS | PHARMACOLOGICAL VALIDATION | SCHISTOSOMA-MANSONI | PROTEIN-KINASE | ALZHEIMERS-DISEASE | 5 INHIBITOR ANALOGS | MIRACIDIAL TRANSFORMATION | TRYPANOSOMA-BRUCEI PHOSPHODIESTERASES | CONSERVED REGIONS UCRS | PARASITOLOGY | TROPICAL MEDICINE | CAMP-SPECIFIC PHOSPHODIESTERASES | Schistosoma mansoni - drug effects | Schistosoma mansoni - physiology | Catalytic Domain | Caenorhabditis elegans - genetics | Schistosoma mansoni - anatomy & histology | Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics | Phosphodiesterase 4 Inhibitors - pharmacology | Animals | Caenorhabditis elegans - drug effects | Animals, Genetically Modified - genetics | Anthelmintics - pharmacology | Cloning, Molecular | Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism | Locomotion - drug effects | Caenorhabditis elegans | Schistosomiasis | Care and treatment | Lung diseases, Obstructive | Genetic aspects | Research | Phosphodiesterases | Alzheimer's disease | Asthma | Drugs | Transgenic | Phosphodiesterase IV | Genomes | Parasites | Nucleotides | Drug development | Kinases | Gene sequencing | Parasitic diseases | Tropical environment | Degeneration | Chronic obstructive pulmonary disease | cDNA | Aquatic invertebrates | Catalysis | Phosphodiesterase | Spurs | 3',5'-Cyclic-nucleotide phosphodiesterase | Lung diseases | Catechol | Gene expression | Diseases | Inhibitors | DNA | Obstructive lung disease | Nematodes | Hypothermia | Lines
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6. Full Text Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency
by Richmond, Bradley W and Brucker, Robert M and Han, Wei and Du, Rui-Hong and Zhang, Yongqin and Cheng, Dong-Sheng and Gleaves, Linda and Abdolrasulnia, Rasul and Polosukhina, Dina and Clark, Peter E and Bordenstein, Seth R and Blackwell, Timothy S and Polosukhin, Vasiliy V
Nature Communications, ISSN 2041-1723, 04/2016, Volume 7, Issue 1, p. 11240
Mechanisms driving persistent airway inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. As secretory immunoglobulin A... 
OBSTRUCTIVE PULMONARY-DISEASE | NONTYPABLE HAEMOPHILUS-INFLUENZAE | MUCOSAL IMMUNITY | INFLAMMATION | MULTIDISCIPLINARY SCIENCES | EMPHYSEMA | SECRETORY IGA | CIGARETTE-SMOKE | ADAPTIVE IMMUNE-RESPONSES | ROFLUMILAST | EXPRESSION | Lung - microbiology | Respiratory Mucosa - drug effects | Pulmonary Disease, Chronic Obstructive - microbiology | Humans | NF-kappa B - immunology | Matrix Metalloproteinase 12 - genetics | Airway Remodeling - immunology | Receptors, Polymeric Immunoglobulin - immunology | Pulmonary Emphysema - microbiology | Respiratory Mucosa - pathology | Respiratory Mucosa - microbiology | Aging - immunology | Immunoglobulin A, Secretory - genetics | Respiratory Mucosa - immunology | Pulmonary Emphysema - genetics | Benzamides - pharmacology | Cyclopropanes - pharmacology | Disease Models, Animal | Pulmonary Disease, Chronic Obstructive - genetics | Lung - pathology | Microbiota - immunology | Receptors, Polymeric Immunoglobulin - deficiency | Matrix Metalloproteinase 12 - immunology | Mice, Inbred C57BL | Gene Expression Regulation | Leukocyte Elastase - genetics | Pulmonary Emphysema - drug therapy | Receptors, Polymeric Immunoglobulin - genetics | Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics | Immunity, Innate | Phosphodiesterase 4 Inhibitors - pharmacology | Pulmonary Emphysema - immunology | Aging - pathology | Mice, Knockout | Host-Pathogen Interactions | Animals | NF-kappa B - genetics | Aminopyridines - pharmacology | Lung - drug effects | Cyclic Nucleotide Phosphodiesterases, Type 4 - immunology | Mice | Leukocyte Elastase - immunology | Pulmonary Disease, Chronic Obstructive - immunology | Lung - immunology | Pulmonary Disease, Chronic Obstructive - drug therapy
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7. Full Text Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center
by Freund, Yvonne R and Akama, Tsutomu and Alley, M.R.K and Antunes, Joana and Dong, Chen and Jarnagin, Kurt and Kimura, Richard and Nieman, James A and Maples, Kirk R and Plattner, Jacob J and Rock, Fernando and Sharma, Rashmi and Singh, Rajeshwar and Sanders, Virginia and Zhou, Yasheen
FEBS Letters, ISSN 0014-5793, 09/2012, Volume 586, Issue 19, pp. 3410 - 3414
► Novel boron-containing small molecule inhibitors of phosphodiesterase 4. ► Co-crystal structure shows unique binding compared to catechol inhibitors. ► Boron... 
Cytokine inhibition | Phenoxybenzoxaborole | PDE4 | Crystal structure | phosphodiesterase 4 | NUCLEOTIDE | BIOPHYSICS | BIOCHEMISTRY & MOLECULAR BIOLOGY | ALPHA | ROFLUMILAST | SELECTIVITY | CELL BIOLOGY | Humans | Anti-Inflammatory Agents, Non-Steroidal - chemistry | Crystallography, X-Ray | Isoenzymes - chemistry | Anti-Inflammatory Agents, Non-Steroidal - pharmacology | Metals - chemistry | Isoenzymes - metabolism | Leukocytes, Mononuclear - immunology | Phosphodiesterase Inhibitors - chemistry | Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism | Cyclic Nucleotide Phosphodiesterases, Type 4 - chemistry | Binding, Competitive | Boron Compounds - chemistry | Recombinant Proteins - metabolism | Boron Compounds - pharmacology | Catalytic Domain | Recombinant Proteins - antagonists & inhibitors | Leukocytes, Mononuclear - drug effects | Isoenzymes - genetics | Bridged Bicyclo Compounds, Heterocyclic - chemistry | Models, Molecular | Phosphodiesterase Inhibitors - pharmacology | Recombinant Proteins - chemistry | Recombinant Proteins - genetics | Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics | Bridged Bicyclo Compounds, Heterocyclic - pharmacology | Kinetics | In Vitro Techniques | Cytokines - biosynthesis | Isoenzymes - antagonists & inhibitors | Enzymes | Catechin | Enzyme inhibitors | Crystals | Laminated metals | Chemical properties | Structure
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8. Full Text The DISC1 pathway modulates expression of neurodevelopmental, synaptogenic and sensory perception genes
by Hennah, William and Porteous, David
PLoS ONE, ISSN 1932-6203, 03/2009, Volume 4, Issue 3, p. e4906
Background: Genetic and biological evidence supports a role for DISC1 across a spectrum of major mental illnesses, including schizophrenia and bipolar... 
BIOLOGY | Cyclic Nucleotide Phosphodiesterases, Type 3 - genetics | Genetic Predisposition to Disease | Microtubule-Associated Proteins - genetics | Microtubule-Associated Proteins - metabolism | Synapses - physiology | Humans | Mental Disorders - metabolism | Gene Expression Regulation | Perception - physiology | Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics | Gene Regulatory Networks | Nerve Tissue Proteins - genetics | Nerve Tissue Proteins - metabolism | Mental Disorders - genetics | Cyclic Nucleotide Phosphodiesterases, Type 3 - metabolism | Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism | Databases, Factual | Proteins | Schizophrenia | Bipolar disorder | Gene expression | Genes | Neurophysiology | Neuroimaging | Haplotypes | Brain | Neurosciences | Target recognition | Ontology | Mental disorders | Genomics | Genomes | Biology | Mental depression | Drug development | Sensory perception | Psychosis | Consortia | Phenomenology | Illnesses | Genetics | Trends | Disc1 protein | Phosphodiesterase | Studies | Public domain | Genetic variance | Data sets | Cytoskeleton | Perception | Mutation
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9. Full Text RNA interference‐mediated phosphodiesterase 4D splice variants knock‐down in the prefrontal cortex produces antidepressant‐like and cognition‐enhancing effects
by Wang, Zhen‐Zhen and Zhang, Yi and Liu, Yan‐Qin and Zhao, Nan and Zhang, You‐Zhi and Yuan, Li and An, Lei and Li, Jing and Wang, Xiao‐Yun and Qin, Juan‐Juan and Wilson, Steven P and O'Donnell, James M and Zhang, Han‐Ting and Li, Yun‐Feng
British Journal of Pharmacology, ISSN 0007-1188, 02/2013, Volume 168, Issue 4, pp. 1001 - 1014
BACKGROUND AND PURPOSE Phosphodiesterase 4 (PDE4) inhibitors produce potent antidepressant-like and cognition-enhancing effects. However, their clinical... 
RNA | cognition | antidepressant | phosphodiesterase | interference | cAMP | dendritic complexity | phosphodiesterase 4D | RNA interference | LONG-TERM-MEMORY | DENDRITIC MORPHOLOGY | HUMAN BRAIN | IMPROVES MEMORY | ELEMENT-BINDING PROTEIN | PDE4 INHIBITORS | STEROID SULFATASE GENES | MESSENGER-RNA | THERAPEUTIC TARGET | PHARMACOLOGY & PHARMACY | RAT HIPPOCAMPUS | RNA, Small Interfering - genetics | Depression - physiopathology | Humans | Male | Gene Knockdown Techniques | RNA Interference | Phosphodiesterase 4 Inhibitors - adverse effects | HEK293 Cells | Cognition - physiology | Lentivirus - genetics | Prefrontal Cortex - enzymology | Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism | Cyclic AMP - metabolism | Real-Time Polymerase Chain Reaction | Maze Learning - physiology | Phosphodiesterase 4 Inhibitors - therapeutic use | Behavior, Animal - physiology | Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics | Blotting, Western | Depression - enzymology | Antidepressive Agents - therapeutic use | Vomiting - chemically induced | Animals | Depression - prevention & control | Mice | Antidepressive Agents - adverse effects | Genetic Vectors | Cognition | Gastrointestinal agents | Antidepressants | Health aspects | Depression, Mental | Cognition & reasoning | Rodents | Index Medicus | Research Papers
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10. Full Text Enhanced long-term potentiation and impaired learning in phosphodiesterase 4D-knockout (PDE4D(-/-)) mice
by Rutten, K and Misner, D.L and Works, M and Blokland, A and Novak, T.J and Santarelli, L and Wallace, T
European Journal of Neuroscience, ISSN 0953-816X, 01/2008, Volume 28, Issue 3, pp. 625 - 632
Elevation of intracellular cyclic adenosine monophosphate (cAMP) concentrations and subsequent regulation of downstream target gene expression through... 
LTP | Mouse | cAMP | Gene knockout | PDE4 | Fear conditioning | REQUIRES PROTEIN-SYNTHESIS | HIPPOCAMPAL CA1 NEURONS | fear conditioning | DEPENDENT MEMORY | SYNAPTIC PLASTICITY | NEUROSCIENCES | ROLIPRAM | gene knockout | mouse | MEMORY CONSOLIDATION | MOUSE MODEL | REDUCED SENSITIVITY | PDE4B ENZYME | Motor Activity - physiology | Synaptic Transmission - physiology | Isoenzymes - genetics | Mice, Inbred C57BL | Electrophysiology | Behavior, Animal - physiology | Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics | Fear - physiology | Conditioning, Classical - physiology | Mice, Knockout | Learning - physiology | Animals | Neuronal Plasticity - physiology | Isoenzymes - metabolism | Long-Term Potentiation - physiology | Mice | Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism | Memory - physiology | Esterases
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