ArticleDiabetes2012
Protein kinase cβ phosphorylates occludin regulating tight junction trafficking in vascular endothelial growth factor-induced permeability in vivo.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 164 citations in OpenAlex.
- Vascular Endothelial Barrier in Salivary Glands: From Physiological Regulation to Pathological Impairment of Secretion.International journal of molecular sciences · 2026Review
- Oxidative Stress in Diabetic Retinopathy: Pathogenic Mechanisms, Biomarkers and Clinical Implications.Antioxidants (Basel, Switzerland) · 2026Review
- Occludin-mediated barrier dysfunction and its role in cardiovascular and cerebrovascular pathogenesis.Frontiers in cardiovascular medicine · 2026Review
- Occludin acts as a dynein adaptor regulating permeability and collateral angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Breakdown of Neurovascular Barriers: Molecular Mechanisms of Tight Junction Dysfunction.Molecular neurobiology · 2025Review
- NADPH oxidase 1-PKCδ-dependent ZO-1 phosphorylation mediates IL-33-induced inner blood-retinal barrier disruption in proliferative retinopathies.American journal of physiology. Cell physiology · 2025Article
- Decoding Allergic Conjunctivitis: Latest Perspectives on Etiological Drivers and Immunopathological Mechanisms.Clinical reviews in allergy & immunology · 2025Review
- Retinal Gatekeepers: Molecular Mechanism and Therapeutic Role of Cysteine and Selenocysteine.Biomolecules · 2025Review
- Deficiency in N-cadherin-Akt3 signaling impairs the blood-brain barrier.Cell reports · 2025Article
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Regulation of BzATP-Induced Blood-Brain Barrier Endothelial Cell Hyperpermeability by NLRP3 Inflammasome Inhibition.Microcirculation (New York, N.Y. : 1994) · 2025Article
- Protein kinase C and endothelial dysfunction in select vascular diseases.Frontiers in cardiovascular medicine · 2025Review
- Deciphering the impact of ABCA4 genetic variants of unknown significance in inherited retinal disease through computational and functional approaches.Advances in protein chemistry and structural biology · 2025Review
- Research progress on Nrf2 intervention in the treatment of diabetic retinopathy.Frontiers in endocrinology · 2025Review
- Sialyl Lewis X decorated integrin α3 on small extracellular vesicles promotes metastasis of bladder cancer via enhancing vascular permeability.Angiogenesis · 2024Article
- Transcription and post-translational mechanisms: dual regulation of adiponectin-mediated Occludin expression in diabetes.Cell & bioscience · 2024Article
- Microvascular destabilization and intricated network of the cytokines in diabetic retinopathy: from the perspective of cellular and molecular components.Cell & bioscience · 2024Review
- Effect of High-Sucrose Diet on the Occurrence and Progression of Diabetic Retinopathy and Dietary Modification Strategies.Nutrients · 2024Review
- Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results.Nature medicine · 2024Article
- Occludin: a gatekeeper of brain Infection by HIV-1.Fluids and barriers of the CNS · 2023Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Vascular endothelial growth factor (VEGF)-induced breakdown of the blood-retinal barrier requires protein kinase C (PKC)β activation. However, the molecular mechanisms related to this process remain poorly understood. In this study, the role of occludin phosphorylation and ubiquitination downstream of PKCβ activation in tight junction (TJ) trafficking and endothelial permeability was investigated. Treatment of bovine retinal endothelial cells and intravitreal injection of PKCβ inhibitors as well as expression of dominant-negative kinase was used to determine the contribution of PKCβ to endothelial permeability and occludin phosphorylation at Ser490 detected with a site-specific antibody. In vitro kinase assay was used to demonstrate direct occludin phosphorylation by PKCβ. Ubiquitination was measured by immunoblotting after occludin immunoprecipitation. Confocal microscopy revealed organization of TJ proteins. The results reveal that inhibition of VEGF-induced PKCβ activation blocks occludin Ser490 phosphorylation, ubiquitination, and TJ trafficking in retinal vascular endothelial cells both in vitro and in vivo and prevents VEGF-stimulated vascular permeability. Occludin Ser490 is a direct target of PKCβ, and mutating Ser490 to Ala (S490A) blocks permeability downstream of PKCβ. Therefore, PKCβ activation phosphorylates occludin on Ser490, leading to ubiquitination required for VEGF-induced permeability. These data demonstrate a novel mechanism for PKCβ targeted inhibitors in regulating vascular permeability.
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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.