ArticleThe Journal of biological chemistry2019
Cx43 phosphorylation-mediated effects on ERK and Akt protect against ischemia reperfusion injury and alter the stability of the stress-inducible protein NDRG1.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Sub-millivolt voltage imaging reveals gap junction-mediated bioelectric contact inhibition.Nature communications · 2026Article
- Article
- Ponatinib confers adult human cardiomyocyte toxicity via inhibition of AKT signaling.Physiological reports · 2026Article
- Intricacies of PKB/Akt Activity after Sciatic Nerve Damage: A Comprehensive Review.Current protein & peptide science · 2026Review
- Identification of Anoikis-Related Genes in Chronic Kidney Disease Based on Bioinformatics Analysis Combined with Experimental Validation.Journal of inflammation research · 2025Article
- Casein Kinase 1 Phosphomimetic Mutations Negatively Impact Connexin-43 Gap Junctions in Human Pluripotent Stem Cell-Derived Cardiomyocytes.Biomolecules · 2024Article
- Channel Behavior and Voltage Gating of a Cx43 Mutant Simulating Preconditioning.Bioelectricity · 2023Article
- Connexin 43: An Interface Connecting Neuroinflammation to Depression.Molecules (Basel, Switzerland) · 2023Review
- Connexin 43 hyper-phosphorylation at serine 282 triggers apoptosis in rat cardiomyocytes via activation of mitochondrial apoptotic pathway.Acta pharmacologica Sinica · 2022Article
- GJA1-20k and Mitochondrial Dynamics.Frontiers in physiology · 2022Review
- Cellular mechanisms of connexin-based inherited diseases.Trends in cell biology · 2022Review
- Recent advances in connexin gap junction biology.Faculty reviews · 2022Review
- Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model.International journal of molecular sciences · 2021Article
- LncRNA AK020546 protects against cardiac ischemia-reperfusion injury by sponging miR-350-3p.Aging · 2021Article
- Connexin 43 phosphorylation by casein kinase 1 is essential for the cardioprotection by ischemic preconditioning.Basic research in cardiology · 2021Article
- Constitutive activation of ERK1/2 signaling protects against myocardial ischemia via inhibition of mitochondrial fragmentation in the aging heart.Annals of translational medicine · 2021Article
- Article
- Src Regulation of Cx43 Phosphorylation and Gap Junction Turnover.Biomolecules · 2020Article
- Restoration of Adiponectin-Connexin43 Signaling Mitigates Myocardial Inflammation and Dysfunction in Diabetic Female Rats.Journal of cardiovascular pharmacology · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Gap junctions contain intercellular channels that enable intercellular communication of small molecules while also serving as a signaling scaffold. Connexins, the proteins that form gap junctions in vertebrates, are highly regulated and typically have short (<2 h) half-lives. Connexin43 (Cx43), the predominate connexin in the myocardium and epithelial tissues, is phosphorylated on more than a dozen serine residues and interacts with a variety of protein kinases. These interactions regulate Cx43 and gap junction formation and stability. Casein kinase 1 (CK1)-mediated phosphorylation of Cx43 promotes gap junction assembly. Using murine knock-in technology and quantitative PCR, immunoblotting, and immunoprecipitation assays, we show here that mutation of the CK1 phosphorylation sites in Cx43 reduces the levels of total Cx43 in the myocardium and increases Cx43 phosphorylation on sites phosphorylated by extracellular signal-regulated kinase (ERK). In aged myocardium, we found that, compared with WT Cx43, mutant Cx43 expression increases ERK activation, phosphorylation of Akt substrates, and protection from ischemia-induced injury. Our findings also uncovered that Cx43 interacts with the hypoxia-inducible protein N-Myc downstream-regulated gene 1 protein (NDRG1) and that Cx43 phosphorylation status controls this interaction and dramatically affects NDRG1 stability. We propose that, in addition to altering gap junction stability, Cx43 phosphorylation directly and dynamically regulates cellular signaling through ERK and Akt in response to ischemic injury. We conclude that gap junction-dependent NDRG1 regulation might explain some cellular responses to hypoxia.
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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.