ArticleCell communication and signaling : CCS2013
CK2-dependent phosphorylation of occludin regulates the interaction with ZO-proteins and tight junction integrity.
Article in Cell communication and signaling : CCS, 2013. 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, 46 citations in OpenAlex.
- Review
- Endothelial barrier and sepsis: mechanisms and potential therapeutic strategies.Military Medical Research · 2026Review
- Keratinocytes regulate intraepithelial lymphocytes homing and mediate mucosal barrier integrity via JAK2/STAT3 signaling in oral lichen planus.Frontiers in immunology · 2026Article
- Impacts of conditionally essential amino acids, cysteine, and tyrosine on intestinal inflammation in celiac disease.Amino acids · 2025Review
- CK2 derived from brain microvascular endothelial cells induces astrocyte inflammatory response in Escherichia coli-induced meningitis.PLoS pathogens · 2025Article
- Deficiency in N-cadherin-Akt3 signaling impairs the blood-brain barrier.Cell reports · 2025Article
- Occludin: a gatekeeper of brain Infection by HIV-1.Fluids and barriers of the CNS · 2023Review
- Influence of Auditory Integrative Training on Casein Kinase 2 and Its Impact on Behavioral and Social Interaction in Children with Autism Spectrum Disorder.Current issues in molecular biology · 2023Article
- Transgenic animal models to explore and modulate the blood brain and blood retinal barriers of the CNS.Fluids and barriers of the CNS · 2022Review
- Serine 408 phosphorylation is a molecular switch that regulates structure and function of the occludin α-helical bundle.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- CK2 and the Hallmarks of Cancer.Biomedicines · 2022Review
- Synaptopodin stress fiber and contractomere at the epithelial junction.The Journal of cell biology · 2022Article
- Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice.The Journal of clinical investigation · 2020Article
- Tight Junctions in Cell Proliferation.International journal of molecular sciences · 2019Review
- The Blood-Brain Barrier and Its Intercellular Junctions in Age-Related Brain Disorders.International journal of molecular sciences · 2019Review
- Tight junction proteins at the blood-brain barrier: far more than claudin-5.Cellular and molecular life sciences : CMLS · 2019Article
- Article
- Phosphorylation hotspot in the C-terminal domain of occludin regulates the dynamics of epithelial junctional complexes.Journal of cell science · 2018Article
- Cell Biology of Tight Junction Barrier Regulation and Mucosal Disease.Cold Spring Harbor perspectives in biology · 2018Review
- Phosphorylation of tight junction transmembrane proteins: Many sites, much to do.Tissue barriers · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCasein kinase 2 (CK2) is a ubiquitously expressed Ser/Thr kinase with multiple functions in the regulation of cell proliferation and transformation. In targeting adherens and tight junctions (TJs), CK2 modulates the strength and dynamics of epithelial cell-cell contacts. Occludin previously was identified as a substrate of CK2, however the functional consequences of CK2-dependent occludin phosphorylation on TJ function were unknown.
resultsHere, we present evidence that phosphorylation of a Thr400-XXX-Thr404-XXX-Ser408 motif in the C-terminal cytoplasmic tail of human occludin regulates assembly/disassembly and barrier properties of TJs. In contrast to wildtype and T400A/T404A/S408A-mutated occludin, a phospho-mimetic Occ-T400E/T404E/S408E construct was impaired in binding to ZO-2. Interestingly, pre-phosphorylation of a GST-Occ C-terminal domain fusion protein attenuated binding to ZO-2, whereas, binding to ZO-1 was not affected. Moreover, Occ-T400E/T404E/S408E showed delayed reassembly into TJs in Ca2+-switch experiments. Stable expression of Occ-T400E/T404E/S408E in MDCK C11 cells augments barrier properties in enhancing paracellular resistance in two-path impedance spectroscopy, whereas expression of wildtype and Occ-T400A/T404A/S408A did not affect transepithelial resistance.
conclusionsThese results suggest an important role of CK2 in epithelial tight junction regulation. The occludin sequence motif at amino acids 400-408 apparently represents a hotspot for Ser/Thr-kinase phosphorylation and depending on the residue(s) which are phosphorylated it differentially modulates the functional properties of the TJ.
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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.