ArticleBritish journal of pharmacology2000
Sub-family selective actions in the ability of Erk2 MAP kinase to phosphorylate and regulate the activity of PDE4 cyclic AMP-specific phosphodiesterases.
Article in British journal of pharmacology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 168 citations in OpenAlex.
- Inhibition of adipocyte lipolysis by vaspin impairs thermoregulation in vivo.Nature communications · 2025Article
- Posttranslational modifications of phosphodiesterase type 4 enzymes represent novel points for therapeutic targeting.The FEBS journal · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Review
- PDE4B Missense Variant Increases Susceptibility to Post-traumatic Stress Disorder-Relevant Phenotypes in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated GMolecular pharmacology · 2024Review
- Phosphodiesterase 4 is overexpressed in keloid epidermal scars and its inhibition reduces keratinocyte fibrotic alterations.Molecular medicine (Cambridge, Mass.) · 2024Article
- PDE4D: A Multipurpose Pharmacological Target.International journal of molecular sciences · 2024Review
- Therapeutic perspectives on PDE4B inhibition in adipose tissue dysfunction and chronic liver injury.Expert opinion on therapeutic targets · 2024Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Phosphodiesterase-4 Inhibition in Parkinson's Disease: Molecular Insights and Therapeutic Potential.Cellular and molecular neurobiology · 2023Review
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Computational investigation of the dynamic control of cAMP signaling by PDE4 isoform types.Biophysical journal · 2022Article
- PAN-selective inhibition of cAMP-phosphodiesterase 4 (PDE4) induces gastroparesis in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Cardiac Cyclic Nucleotide Phosphodiesterases: Roles and Therapeutic Potential in Heart Failure.Cardiovascular drugs and therapy · 2020Review
- Review
- Mitogen-activated protein kinase regulation of the phosphodiesterase RegA in earlyMicrobiology (Reading, England) · 2020Article
- Small-molecule allosteric activators of PDE4 long form cyclic AMP phosphodiesterases.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Structural Analysis of Hippocampal Kinase Signal Transduction.ACS chemical neuroscience · 2018Article
- Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System.Journal of cardiovascular development and disease · 2018Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Expressed in intact cells and in vitro, PDE4B and PDE4C isoenzymes of cyclic nucleotide phosphodiesterase (PDE), in common with PDE4D isoenzymes, are shown to provide substrates for C-terminal catalytic unit phosphorylation by the extracellular signal-regulated kinase Erk2 (p42(MAPK)). In contrast, PDE4A isoenzymes do not provide substrates for C-terminal catalytic unit phosphorylation by Erk2. Mutant PDE4 enzymes were generated to show that Erk2 phosphorylation occurs at a single, cognate serine residue located within the C-terminal portion of the PDE4 catalytic unit. PDE4 long-form isoenzymes were markedly inhibited by Erk2 phosphorylation. The short-form PDE4B2 isoenzyme was activated by Erk2 phosphorylation. These functional changes in PDE activity were mimicked by mutation of the target serine for Erk2 phosphorylation to the negatively charged amino acid, aspartic acid. Epidermal growth factor (EGF) challenge caused diametrically opposed changes in cyclic AMP levels in COS1 cells transfected to express the long PDE4B1 isoenzyme compared to cells expressing the short PDE4B2 isoenzyme. We suggest that PDE4 enzymes may provide a pivotal point for integrating cyclic AMP and Erk signal transduction in cells with 4 genes encoding enzymes that are either insensitive to Erk2 action or may either be activated or inhibited. This indicates that PDE4 isoenzymes have distinct functional roles, giving credence to the notion that distinct therapeutic benefits may accrue using either PDE4 subfamily or isoenzyme-selective inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.