ArticleThe Biochemical journal2017
Identification of a multifunctional docking site on the catalytic unit of phosphodiesterase-4 (PDE4) that is utilised by multiple interaction partners.
Article in The Biochemical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Posttranslational modifications of phosphodiesterase type 4 enzymes represent novel points for therapeutic targeting.The FEBS journal · 2025Review
- Stress and Inflammation Target Dorsolateral Prefrontal Cortex Function: Neural Mechanisms Underlying Weakened Cognitive Control.Biological psychiatry · 2025Review
- cAMP-phosphodiesterase 4D7 (PDE4D7) forms a cAMP signalosome complex with DHX9 and is implicated in prostate cancer progression.Molecular oncology · 2024Article
- Phosphodiesterase 4D activity in acrodysostosis-associated neural pathology: too much or too little?Brain communications · 2024Review
- Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia.Biological psychiatry · 2022Review
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.Journal of molecular and cellular cardiology · 2022Article
- Mitogen-activated protein kinase-activated protein kinase-2 (MK2) and its role in cell survival, inflammatory signaling, and migration in promoting cancer.Molecular carcinogenesis · 2022Article
- Neuromodulation of prefrontal cortex cognitive function in primates: the powerful roles of monoamines and acetylcholine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Review
- Studies of aging nonhuman primates illuminate the etiology of early-stage Alzheimer's-like neuropathology: An evolutionary perspective.American journal of primatology · 2021Review
- The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex.Molecular psychiatry · 2021Review
- Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.International journal of molecular sciences · 2020Article
- Mapping Phosphodiesterase 4D (PDE4D) in Macaque Dorsolateral Prefrontal Cortex: Postsynaptic Compartmentalization in Layer III Pyramidal Cell Circuits.Frontiers in neuroanatomy · 2020Article
- Alzheimer's-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Loss of Prefrontal Cortical Higher Cognition with Uncontrollable Stress: Molecular Mechanisms, Changes with Age, and Relevance to Treatment.Brain sciences · 2019Review
- A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling.Translational psychiatry · 2019Article
- Mechanisms underlying the role of DISC1 in synaptic plasticity.The Journal of physiology · 2018Review
- PDE4-Mediated cAMP Signalling.Journal of cardiovascular development and disease · 2018Review
- The Prognostic PDE4D7 Score in a Diagnostic Biopsy Prostate Cancer Patient Cohort with Longitudinal Biological Outcomes.Prostate cancer · 2018Article
- Osthole-Mediated Inhibition of Neurotoxicity Induced by Ropivacaine via Amplification of the Cyclic Adenosine Monophosphate Signaling Pathway.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Cyclic AMP (cAMP)-specific phosphodiesterase-4 (PDE4) enzymes underpin compartmentalised cAMP signalling by localising to distinct signalling complexes. PDE4 long isoforms can be phosphorylated by mitogen-activated protein kinase-activated protein kinase 2 (MK2), which attenuates activation of such enzymes through their phosphorylation by protein kinase A. Here we show that MK2 interacts directly with PDE4 long isoforms and define the sites of interaction. One is a unique site that locates within the regulatory upstream conserved region 1 (UCR1) domain and contains a core Phe141, Leu142 and Tyr143 (FLY) cluster (PDE4A5 numbering). Located with the second site is a critical core Phe693, Glu694, Phe695 (FQF) motif that is also employed in the sequestering of PDE4 long forms by an array of other signalling proteins, including the signalling scaffold β-arrestin, the tyrosyl kinase Lyn, the SUMOylation E2 ligase UBC9, the dynein regulator Lis1 (PAFAH1B1) and the protein kinase Erk. We propose that the FQF motif lies at the heart of a multifunctional docking (MFD) site located within the PDE4 catalytic unit. It is clear from our data that, as well as aiding fidelity of interaction, the MFD site confers exclusivity of binding between PDE4 and a single specific partner protein from the cohort of signalling proteins whose interaction with PDE4 involves the FQF motif.
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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.