ArticleMolecular biology of the cell2015
Connexin43 phosphorylation by PKC and MAPK signals VEGF-mediated gap junction internalization.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 85 citations in OpenAlex.
- Article
- Molecular Modeling and Dynamics of a Complete Connexin-43 Gap Junction Channel in Various Phosphorylation States.The journal of physical chemistry. B · 2026Article
- Injury-induced connexin 43 expression regulates endothelial wound healing.American journal of physiology. Heart and circulatory physiology · 2025Article
- Control of epithelial homeostasis by apical polarity: it takes a network.Biochemical Society transactions · 2025Article
- OXTR-mediated signaling in astrocytes contributes to anxiolysis.Molecular psychiatry · 2025Article
- Mild hypothermia (35°C) reduces myocardial ischemia-reperfusion injury and attenuates hypoxia induced apoptosis of H9C2 cardiomyocytes by changing the phosphorylation level of Connexin43 (Cx43) protein.African health sciences · 2025Article
- Astrocyte regulation of behavioral outputs: the versatile roles of calcium.Frontiers in cellular neuroscience · 2025Review
- Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes.eLife · 2024Article
- The effect of CGRP and SP and the cell signaling dialogue between sensory neurons and endothelial cells.Biological research · 2024Article
- Understanding the Role of Connexins in Hepatocellular Carcinoma: Molecular and Prognostic Implications.Cancers · 2024Review
- Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis.Circulation research · 2024Article
- Interplay between paclitaxel, gap junctions, and kinases: unraveling mechanisms of action and resistance in cancer therapy.Molecular biology reports · 2024Review
- Connexins 30 and 43 expression changes in relation to age-related hearing loss.Hearing research · 2024Article
- The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients.Frontiers in neuroscience · 2024Review
- Connexin 43 Phosphorylation: Implications in Multiple Diseases.Molecules (Basel, Switzerland) · 2023Review
- Cohesin: an emerging master regulator at the heart of cardiac development.Molecular biology of the cell · 2023Article
- Analgesics can affect the sensitivity of temozolomide to glioma chemotherapy through gap junction.Medical oncology (Northwood, London, England) · 2023Article
- Ubiquitin-Related Modifier 1 (URM-1) Modulates Cx43 in Breast Cancer Cell Lines.International journal of molecular sciences · 2023Article
- The roles of connexins and gap junctions in the progression of cancer.Cell communication and signaling : CCS · 2023Review
- Omarigliptin Protects the Integrity of the Blood-Brain Barrier After Intracerebral Hemorrhage in Mice.Journal of inflammation research · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Gap junctions (GJs) exhibit a complex modus of assembly and degradation to maintain balanced intercellular communication (GJIC). Several growth factors, including vascular endothelial growth factor (VEGF), have been reported to disrupt cell-cell junctions and abolish GJIC. VEGF directly stimulates VEGF-receptor tyrosine kinases on endothelial cell surfaces. Exposing primary porcine pulmonary artery endothelial cells (PAECs) to VEGF for 15 min resulted in a rapid and almost complete loss of connexin43 (Cx43) GJs at cell-cell appositions and a concomitant increase in cytoplasmic, vesicular Cx43. After prolonged incubation periods (60 min), Cx43 GJs reformed and intracellular Cx43 were restored to levels observed before treatment. GJ internalization correlated with efficient inhibition of GJIC, up to 2.8-fold increased phosphorylation of Cx43 serine residues 255, 262, 279/282, and 368, and appeared to be clathrin driven. Phosphorylation of serines 255, 262, and 279/282 was mediated by MAPK, whereas serine 368 phosphorylation was mediated by PKC. Pharmacological inhibition of both signaling pathways significantly reduced Cx43 phosphorylation and GJ internalization. Together, our results indicate that growth factors such as VEGF activate a hierarchical kinase program--including PKC and MAPK--that induces GJ internalization via phosphorylation of well-known regulatory amino acid residues located in the Cx43 C-terminal tail.
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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 Socratic graph.