ArticlePloS one2014
PKA compartmentalization via AKAP220 and AKAP12 contributes to endothelial barrier regulation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 47 citations in OpenAlex.
- Schizophrenia-Related Synaptic Dysfunction and Abnormal Sensorimotor Gating in Akap11-Deficient Mice.Schizophrenia bulletin · 2026Article
- The IRE1Cell stress · 2026Article
- CD109 Drives Stemness and Chemoresistance in Colorectal Cancer via LRRC8A/AKAP12/PKCα-Mediated STAT3 Activation and WNT Signaling.International journal of biological sciences · 2026Article
- Family-Wide Dysregulation of Phosphodiesterases Alters cAMP/cGMP Microdomains in Thoracic Aortic Aneurysm.Journal of cardiovascular development and disease · 2026Article
- Correlation of autophagy and Alzheimer's disease with special emphasis on the role of phosphodiesterase-4.3 Biotech · 2025Review
- Plakoglobin does not participate in endothelial barrier stabilization mediated by cAMP.Scientific reports · 2025Article
- AKAP12 Variant 1 Knockout Enhances Vascular Endothelial Cell Motility.Journal of vascular research · 2025Article
- Ubiquitin-related gene markers predict immunotherapy response and prognosis in patients with epithelial ovarian carcinoma.Scientific reports · 2024Article
- Plasma cell-free RNA signatures of inflammatory syndromes in children.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Protein Kinase A Inhibitor KT5720 Prevents Endothelial Dysfunctions Induced by High-Dose Irradiation.International journal of molecular sciences · 2024Article
- Article
- Review
- Lack of adducin impairs the stability of endothelial adherens and tight junctions and may be required for cAMP-Rac1-mediated endothelial barrier stabilization.Scientific reports · 2022Article
- Clinical Implication of Phosphodiesterase-4-Inhibition.International journal of molecular sciences · 2022Review
- Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors.Frontiers in genetics · 2022Article
- Review
- ARHGEF18/p114RhoGEF Coordinates PKA/CREB Signaling and Actomyosin Remodeling to Promote Trophoblast Cell-Cell Fusion During Placenta Morphogenesis.Frontiers in cell and developmental biology · 2021Article
- Polarized Proteins in Endothelium and Their Contribution to Function.Journal of vascular research · 2021Review
- Article
- AKAP12 Signaling Complex: Impacts of Compartmentalizing cAMP-Dependent Signaling Pathways in the Heart and Various Signaling Systems.Journal of the American Heart Association · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
cAMP-mediated PKA signaling is the main known pathway involved in maintenance of the endothelial barrier. Tight regulation of PKA function can be achieved by discrete compartmentalization of the enzyme via physical interaction with A-kinase anchoring proteins (AKAPs). Here, we investigated the role of AKAPs 220 and 12 in endothelial barrier regulation. Analysis of human and mouse microvascular endothelial cells as well as isolated rat mesenteric microvessels was performed using TAT-Ahx-AKAPis peptide, designed to competitively inhibit PKA-AKAP interaction. In vivo microvessel hydraulic conductivity and in vitro transendothelial electrical resistance measurements showed that this peptide destabilized endothelial barrier properties, and dampened the cAMP-mediated endothelial barrier stabilization induced by forskolin and rolipram. Immunofluorescence analysis revealed that TAT-Ahx-AKAPis led to both adherens junctions and actin cytoskeleton reorganization. Those effects were paralleled by redistribution of PKA and Rac1 from endothelial junctions and by Rac1 inactivation. Similarly, membrane localization of AKAP220 was also reduced. In addition, depletion of either AKAP12 or AKAP220 significantly impaired endothelial barrier function and AKAP12 was also shown to interfere with cAMP-mediated barrier enhancement. Furthermore, immunoprecipitation analysis demonstrated that AKAP220 interacts not only with PKA but also with VE-cadherin and ß-catenin. Taken together, these results indicate that AKAP-mediated PKA subcellular compartmentalization is involved in endothelial barrier regulation. More specifically, AKAP220 and AKAP12 contribute to endothelial barrier function and AKAP12 is required for cAMP-mediated barrier stabilization.
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