ArticleThe Journal of biological chemistry2012
Activation of Akt, not connexin 43 protein ubiquitination, regulates gap junction stability.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 98 citations in OpenAlex.
- The E3 ubiquitin ligase ITCH negatively regulates intercellular communication via gap junctions by targeting connexin43 for lysosomal degradation.Cellular and molecular life sciences : CMLS · 2024Article
- Post translational modifications of connexin 43 in ventricular arrhythmias after myocardial infarction.Molecular biology reports · 2024Review
- Mechanism of Nardostachyos Radix et Rhizoma-Salidroside in the treatment of premature ventricular beats based on network pharmacology and molecular docking.Scientific reports · 2023Article
- Rat Hepatocytes Mitigate Cadmium Toxicity by Forming Annular Gap Junctions and Degrading Them via Endosome-Lysosome Pathway.International journal of molecular sciences · 2022Article
- Connexins and Glucose Metabolism in Cancer.International journal of molecular sciences · 2022Review
- Gap junctions mediate discrete regulatory steps during fly spermatogenesis.PLoS genetics · 2022Article
- New Insights on the Role of Connexins and Gap Junctions Channels in Adipose Tissue and Obesity.International journal of molecular sciences · 2021Review
- Integrin-Linked Kinase Activation Prevents Ventricular Arrhythmias Induced by Ischemia/Reperfusion Via Inhibition of Connexin 43 Remodeling.Journal of cardiovascular translational research · 2021Article
- Connexins in the Heart: Regulation, Function and Involvement in Cardiac Disease.International journal of molecular sciences · 2021Review
- Staphylococcus aureus impairs cutaneous wound healing by activating the expression of a gap junction protein, connexin-43 in keratinocytes.Cellular and molecular life sciences : CMLS · 2021Article
- Src Regulation of Cx43 Phosphorylation and Gap Junction Turnover.Biomolecules · 2020Article
- Targeting connexin 43 provides anti-inflammatory effects after intracerebral hemorrhage injury by regulating YAP signaling.Journal of neuroinflammation · 2020Article
- A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43.International journal of molecular sciences · 2020Review
- Cardiac β-adrenergic receptor activation mediates distinct and cell type-dependent changes in the expression and distribution of connexin 43.Journal of cellular and molecular medicine · 2020Article
- Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications.Cellular and molecular life sciences : CMLS · 2020Review
- Adenoviral transduction of EGFR into pregnancy-adapted uterine artery endothelial cells remaps growth factor induction of endothelial dysfunction.Molecular and cellular endocrinology · 2020Article
- Resveratrol Sensitizes Colorectal Cancer Cells to Cetuximab by Connexin 43 Upregulation-Induced Akt Inhibition.Frontiers in oncology · 2020Article
- Pannexin 3 ER CaScientific reports · 2019Article
- Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease.International journal of molecular sciences · 2019Review
- The lipidated connexin mimetic peptide SRPTEKT-American journal of physiology. Cell physiology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The pore-forming gap junctional protein connexin 43 (Cx43) has a short (1-3 h) half-life in cells in tissue culture and in whole tissues. Although critical for cellular function in all tissues, the process of gap junction turnover is not well understood because treatment of cells with a proteasomal inhibitor results in larger gap junctions but little change in total Cx43 protein whereas lysosomal inhibitors increase total, mostly nonjunctional Cx43. To better understand turnover and identify potential sites of Cx43 ubiquitination, we prepared constructs of Cx43 with different lysines converted to arginines. However, when transfected into cells, a mutant version of Cx43 with all lysines converted to arginines behaved similarly to wild type in the presence of proteasomal and lysosomal inhibitors, indicating that ubiquitination of Cx43 did not appear to be playing a role in gap junction stability. Through the use of inhibitors and dominant negative constructs, we found that Akt (protein kinase B) activity controlled gap junction stability and was necessary to form larger stable gap junctions. Akt activation was increased upon proteasomal inhibition and resulted in phosphorylation of Cx43 at Akt phosphorylation consensus sites. Thus, we conclude that Cx43 ubiquitination is not necessary for the regulation of Cx43 turnover; rather, Akt activity, probably through direct phosphorylation of Cx43, controls gap junction stability. This linkage of a kinase involved in controlling cell survival and growth to gap junction stability may mechanistically explain how gap junctions and Akt play similar regulatory roles.
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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.