ArticleMolecular biology of the cell2005
Gap junctions regulate extracellular signal-regulated kinase signaling to affect gene transcription.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Connexin 43 C-terminus directly inhibits the hyperphosphorylation of Akt/ERK through protein-protein interactions in glioblastoma.Cancer science · 2018Pooled it
- Pannexins in the musculoskeletal system: new targets for development and disease progression.Bone research · 2024Review
- Loss of Function of the Retinoblastoma Gene Affects Gap Junctional Intercellular Communication and Cell Fate in Osteoblasts.Biology · 2024Article
- Enoxolone suppresses apoptosis in chondrocytes and progression of osteoarthritis via modulating the ERK1/2 signaling pathway.Archives of medical science : AMS · 2024Article
- Connexin43 in Musculoskeletal System: New Targets for Development and Disease Progression.Aging and disease · 2022Article
- A new player in circadian networks: Role of electrical synapses in regulating functions of the circadian clock.Frontiers in physiology · 2022Review
- Bone fracture healing: perspectives according to molecular basis.Journal of bone and mineral metabolism · 2021Review
- Connexins in the Heart: Regulation, Function and Involvement in Cardiac Disease.International journal of molecular sciences · 2021Review
- Connexin 43-Mediated Gap Junction Communication Regulates Ameloblast DifferentiationFrontiers in physiology · 2021Article
- Antagonistic Functions of Connexin 43 during the Development of Primary or Secondary Bone Tumors.Biomolecules · 2020Review
- Connexin43 enhances Wnt and PGE2-dependent activation of β-catenin in osteoblasts.Pflugers Archiv : European journal of physiology · 2019Article
- Gap Junctions and Wnt Signaling in the Mammary Gland: a Cross-Talk?Journal of mammary gland biology and neoplasia · 2019Review
- Connexin43 regulates osteoprotegerin expression via ERK1/2 -dependent recruitment of Sp1.Biochemical and biophysical research communications · 2019Article
- Review
- Molecular signaling in bone cells: Regulation of cell differentiation and survival.Advances in protein chemistry and structural biology · 2019Review
- Targeting of chondrocyte plasticity via connexin43 modulation attenuates cellular senescence and fosters a pro-regenerative environment in osteoarthritis.Cell death & disease · 2018Article
- Non-junctional Cx32 mediates anti-apoptotic and pro-tumor effects via epidermal growth factor receptor in human cervical cancer cells.Cell death & disease · 2017Article
- Gap junctional signaling in pattern regulation: Physiological network connectivity instructs growth and form.Developmental neurobiology · 2017Review
- Astrocytes induce proliferation of oligodendrocyte progenitor cells via connexin 47-mediated activation of the ERK/Id4 pathway.Cell cycle (Georgetown, Tex.) · 2017Article
- BMP Signaling Mediated by BMPR1A in Osteoclasts Negatively Regulates Osteoblast Mineralization Through Suppression of Cx43.Journal of cellular biochemistry · 2017Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Osteoblasts are highly coupled by gap junctions formed by connexin43. Overexpression of connexin45 in osteoblasts results in decreased chemical and electrical coupling and reduces gene transcription from connexin response elements (CxREs) in the osteocalcin and collagen Ialpha1 promoters. Here, we demonstrate that transcription from the gap junction-dependent osteocalcin CxRE is regulated by extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) cascades. Overexpression of a constitutively active mitogen-activated protein kinase kinase (MEK), Raf, or Ras can increase transcription more than twofold of the CxRE, whereas inhibition of MEK or PI3K can decrease transcription threefold from the osteocalcin CxRE. Importantly, disruption of gap junctional communication by overexpression of connexin45 or treatment with pharmacological inhibitors of gap junctions results in reduced Raf, ERK, and Akt activation. The consequence of attenuated gap junction-dependent signal cascade activation is a decrease in Sp1 phosphorylation by ERK, resulting in decreased Sp1 recruitment to the CxRE and inhibited gene transcription. These data establish that ERK/PI3K signaling is required for the optimal elaboration of transcription from the osteocalcin CxRE, and that disruption of gap junctional communication attenuates the ability of cells to respond to an extracellular cue, presumably by limiting the propagation of second messengers among adjacent cells by connexin43-gap junctions.
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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.