ArticleThe FEBS journal2010
Ca2+/calmodulin-stimulated PDE1 regulates the beta-catenin/TCF signaling through PP2A B56 gamma subunit in proliferating vascular smooth muscle cells.
Article in The FEBS journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Association of Circulating Apolipoprotein AI Levels in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis.Frontiers in aging neuroscience · 2022Pooled it
- Single-nucleus transcriptome profiling of skeletal muscle in Diqing Tibetan pigs with distinct body sizes.BMC genomics · 2025Article
- PP2Acα Deficiency in Vascular Smooth Muscle Cells Accelerates Aortic Aneurysm and Dissection by Regulating KLF4 Phosphorylation and Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The perspective of modern transplant science - transplant arteriosclerosis: inspiration derived from mitochondria associated endoplasmic reticulum membrane dysfunction in arterial diseases.International journal of surgery (London, England) · 2025Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Role of PDE10A in vascular smooth muscle cell hyperplasia and pathological vascular remodelling.Cardiovascular research · 2022Article
- Article
- PP2A-dependent TFEB activation is blocked by PIKfyve-induced mTORC1 activity.Molecular biology of the cell · 2022Article
- Role of phosphodiesterase 1 in the pathophysiology of diseases and potential therapeutic opportunities.Pharmacology & therapeutics · 2021Review
- Allosteric activation of PP2A inhibits experimental abdominal aortic aneurysm.Clinical science (London, England : 1979) · 2021Article
- Protein phosphatase 2A - structure, function and role in neurodevelopmental disorders.Journal of cell science · 2021Review
- Endoplasmic Reticulum-Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling.International journal of molecular sciences · 2021Review
- Updates of Recent Vinpocetine Research in Treating Cardiovascular Diseases.Journal of cellular immunology · 2020Article
- PP2A as the Main Node of Therapeutic Strategies and Resistance Reversal in Triple-Negative Breast Cancer.Molecules (Basel, Switzerland) · 2017Review
- Article
- The broken "Off" switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance.BBA clinical · 2016Review
- Cyclic nucleotide phosphodiesterase 1 and vascular aging.Clinical science (London, England : 1979) · 2015Article
- cAMP and Ca²⁺ signaling in secretory epithelia: crosstalk and synergism.Cell calcium · 2014Review
- Apolipoprotein A-I: insights from redox proteomics for its role in neurodegeneration.Proteomics. Clinical applications · 2013Review
- Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration.The Journal of pharmacology and experimental therapeutics · 2012Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The phenotypic change of vascular smooth muscle cells (VSMCs), from a 'contractile' phenotype to a 'synthetic' phenotype, is crucial for pathogenic vascular remodeling in vascular diseases such as atherosclerosis and restenosis. Ca(2+)/calmodulin-stimulated phosphodiesterase 1 (PDE1) isozymes, including PDE1A and PDE1C, play integral roles in regulating the proliferation of synthetic VSMCs. However, the underlying molecular mechanism(s) remain unknown. In this study, we explore the role and mechanism of PDE1 isoforms in regulating β-catenin/T-cell factor (TCF) signaling in VSMCs, a pathway important for vascular remodeling through promoting VSMC growth and survival. We found that inhibition of PDE1 activity markedly attenuated β-catenin/TCF signaling by downregulating β-catenin protein. The effect of PDE1 inhibition on β-catenin protein reduction is exerted via promoting glycogen synthase kinase 3 (GSK3)β activation, β-catenin phosphorylation and subsequent β-catenin protein degradation. Moreover, PDE1 inhibition specifically upregulated phosphatase protein phosphatase 2A (PP2A) B56γ subunit gene expression, which is responsible for the effects of PDE1 inhibition on GSK3β and β-catenin/TCF signaling. Furthermore, the effect of PDE1 inhibition on β-catenin was specifically mediated by PDE1A but not PDE1C isozyme. Interestingly, in synthetic VSMCs, PP2A B56γ, phospho-GSK3β and phospho-β-catenin were all found in the nucleus, suggesting that PDE1A regulates nuclear β-catenin protein stability through the nuclear PP2A-GSK3β-β-catenin signaling axis. Taken together, these findings provide direct evidence for the first time that PP2A B56γ is a critical mediator for PDE1A in the regulation of β-catenin signaling in proliferating VSMCs.
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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.