ArticleBritish journal of pharmacology2002
Long PDE4 cAMP specific phosphodiesterases are activated by protein kinase A-mediated phosphorylation of a single serine residue in Upstream Conserved Region 1 (UCR1).
Article in British journal of pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 259 citations in OpenAlex.
- Conformational Dynamics and Allostery in the cAMP-Protein Kinase A Signalosome.Advances in experimental medicine and biology · 2026Review
- Posttranslational modifications of phosphodiesterase type 4 enzymes represent novel points for therapeutic targeting.The FEBS journal · 2025Review
- The Molecular Mechanism of PDE1 Regulation.Cells · 2025Article
- Chemical, Biochemical, and Structural Similarities and Differences of Dermatological cAMP Phosphodiesterase-IV Inhibitors.The Journal of investigative dermatology · 2025Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- Review
- The β2 adrenergic receptor cross-linked interactome identifies 14-3-3 proteins as regulating the availability of signaling-competent receptors.Molecular pharmacology · 2025Article
- 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
- PDE4D: A Multipurpose Pharmacological Target.International journal of molecular sciences · 2024Review
- cAMP-phosphodiesterase 4D7 (PDE4D7) forms a cAMP signalosome complex with DHX9 and is implicated in prostate cancer progression.Molecular oncology · 2024Article
- The Establishment and Optimization of a Chicken Primordial Germ Cell Induction Model Using Small-Molecule Compounds.Animals : an open access journal from MDPI · 2024Article
- Phosphodiesterase 4D activity in acrodysostosis-associated neural pathology: too much or too little?Brain communications · 2024Review
- The evolution of small molecule enzyme activators.RSC medicinal chemistry · 2023Review
- Phosphodiesterase-4 Inhibition in Parkinson's Disease: Molecular Insights and Therapeutic Potential.Cellular and molecular neurobiology · 2023Review
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Muscarinic acetylcholine receptor-dependent and NMDA receptor-dependent LTP and LTD share the common AMPAR trafficking pathway.iScience · 2023Article
- Article
- Bassoon controls synaptic vesicle release via regulation of presynaptic phosphorylation and cAMP.EMBO reports · 2022Article
- Computational investigation of the dynamic control of cAMP signaling by PDE4 isoform types.Biophysical journal · 2022Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Challenge of COS1 cells with the adenylyl cyclase activator forskolin led to the activation of recombinant PDE4A8, PDE4B1, PDE4C2 and PDE4D5 cAMP-specific phosphodiesterase long isoforms. 2. Forskolin challenge did not activate mutant long PDE4 isoforms where the serine target residue (STR) within the protein kinase A (PKA) consensus phosphorylation site in Upstream Conserved Region 1 (UCR1) was mutated to alanine. 3. The PKA inhibitor, H89, ablated forskolin activation of wild-type long PDE4 isoforms. 4. Activated PKA caused the in vitro phosphorylation of recombinant wild-type long PDE4 isoforms, but not those where the STR was mutated to alanine. 5. An antiserum specific for the phosphorylated form of the STR detected a single immunoreactive band for recombinant long PDE4 isoforms expressed in COS1 cells challenged with forskolin. This was not evident in forskolin-challenged cells treated with H89. Neither was it evident in forskolin-challenged cells expressing long isoforms where the STR had been mutated to alanine. 6. In transfected COS cells challenged with forskolin, only the phosphorylated PDE4D3 long form showed a decrease in mobility in Western blotting analysis. This decreased mobility of PDE4D3 was ablated upon mutation of either of the two serine targets for PKA phosphorylation in this isoform, namely Ser54 in UCR1 and Ser13 in the isoform-specific N-terminal region. 7. Activation by forskolin challenge did not markedly alter the sensitivity of PDE4A8, PDE4B1, PDE4C2 and PDE4D5 to inhibition by rolipram. 8. Long PDE4 isoforms from all four sub-families can be phosphorylated by protein kinase A (PKA). This leads to an increase in their activity and may thus contribute to cellular desensitization processes in cells where these isoforms are selectively expressed.
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