ArticleThe Journal of cell biology2012
PKA and PDE4D3 anchoring to AKAP9 provides distinct regulation of cAMP signals at the centrosome.
Article in The Journal of cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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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
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Genetic and environmental risk factors for dementia in African adults: A systematic review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Centrosome-Signaling Pathway Crosstalk: A Core Hub From Cellular Homeostasis to Disease.Cytoskeleton (Hoboken, N.J.) · 2026Review
- A GPER-PKA-Centrin axis regulates centrosome numbers and centriole integrity in colon cancer cells.Communications biology · 2025Article
- Article
- Centrosomal actin pool levels regulated by localized PKA set the threshold for T cell polarization.EMBO reports · 2025Article
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Intersection of GPCR trafficking and cAMP signaling at endomembranes.The Journal of cell biology · 2025Review
- Review
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration.Nature communications · 2023Article
- Fluorescent biosensors illuminate the spatial regulation of cell signaling across scales.The Biochemical journal · 2023Review
- Genetics of Alzheimer's Disease in the African American Population.Journal of clinical medicine · 2023Review
- Ablation of specific long PDE4D isoforms increases neurite elongation and conveys protection against amyloid-β pathology.Cellular and molecular life sciences : CMLS · 2023Article
- Compartmentalised cAMP signalling in the primary cilium.Frontiers in physiology · 2023Review
- Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Control of the Hedgehog pathway by compartmentalized PKA in the primary cilium.Science China. Life sciences · 2022Review
- A-Kinase Anchoring Protein 9 Promotes Gastric Cancer Progression as a Downstream Effector of Cadherin 1.Journal of oncology · 2022Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Previous work has shown that the protein kinase A (PKA)-regulated phosphodiesterase (PDE) 4D3 binds to A kinase-anchoring proteins (AKAPs). One such protein, AKAP9, localizes to the centrosome. In this paper, we investigate whether a PKA-PDE4D3-AKAP9 complex can generate spatial compartmentalization of cyclic adenosine monophosphate (cAMP) signaling at the centrosome. Real-time imaging of fluorescence resonance energy transfer reporters shows that centrosomal PDE4D3 modulated a dynamic microdomain within which cAMP concentration selectively changed over the cell cycle. AKAP9-anchored, centrosomal PKA showed a reduced activation threshold as a consequence of increased autophosphorylation of its regulatory subunit at S114. Finally, disruption of the centrosomal cAMP microdomain by local displacement of PDE4D3 impaired cell cycle progression as a result of accumulation of cells in prophase. Our findings describe a novel mechanism of PKA activity regulation that relies on binding to AKAPs and consequent modulation of the enzyme activation threshold rather than on overall changes in cAMP levels. Further, we provide for the first time direct evidence that control of cell cycle progression relies on unique regulation of centrosomal cAMP/PKA signals.
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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.