ArticleMolecular biology of the cell2009
Mitochondrial reactive oxygen species mediate GPCR-induced TACE/ADAM17-dependent transforming growth factor-alpha shedding.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- KIN-29 SIK regulates stress-induced sleep through mitochondrial redox signaling.bioRxiv : the preprint server for biology · 2026Article
- Crosstalk of Mast Cells and Natural Killer Cells with Neurons in Chemotherapy-Induced Peripheral Neuropathy.International journal of molecular sciences · 2023Review
- The regulation and function of acetylated high-mobility group box 1 during implantation and decidualization.Frontiers in immunology · 2023Article
- G-Protein Coupled Receptor 35 Induces Intervertebral Disc Degeneration by Mediating the Influx of Calcium Ions and Upregulating Reactive Oxygen Species.Oxidative medicine and cellular longevity · 2022Article
- Cyclosporin A activates human hepatocellular carcinoma (HepG2 cells) proliferation: implication of EGFR-mediated ERK1/2 signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- ADAM17 stabilizes its interacting partner inactive Rhomboid 2 (iRhom2) but not inactive Rhomboid 1 (iRhom1).The Journal of biological chemistry · 2020Article
- Exposure to mold proteases stimulates mucin production in airway epithelial cells through Ras/Raf1/ERK signal pathway.PloS one · 2020Article
- BRET-based assay to monitor EGFR transactivation by the ATBiochemical pharmacology · 2018Article
- NADPH oxidase-generated reactive oxygen species in mature follicles are essential forProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Tumor necrosis factor α-converting enzyme inhibitor attenuates lipopolysaccharide-induced reactive oxygen species and mitogen-activated protein kinase expression in human renal proximal tubule epithelial cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2018Article
- Structural modeling defines transmembrane residues in ADAM17 that are crucial for Rhbdf2-ADAM17-dependent proteolysis.Journal of cell science · 2017Article
- Therapeutic potential of ADAM17 modulation in gastric cancer through regulation of the EGFR and TNF-α signalling pathways.Molecular and cellular biochemistry · 2017Article
- Redox Regulation of Inflammatory Processes Is Enzymatically Controlled.Oxidative medicine and cellular longevity · 2017Review
- Roles of extracellular nucleotides and P2 receptors in ectodomain shedding.Cellular and molecular life sciences : CMLS · 2016Review
- Exosomes: The Link between GPCR Activation and Metastatic Potential?Frontiers in genetics · 2016Review
- Cell-surface receptors transactivation mediated by g protein-coupled receptors.International journal of molecular sciences · 2014Review
- A role for the p75 neurotrophin receptor in axonal degeneration and apoptosis induced by oxidative stress.The Journal of biological chemistry · 2014Article
- Identification of DUOX1-dependent redox signaling through protein S-glutathionylation in airway epithelial cells.Redox biology · 2014Article
- PKCδ and θ possibly mediate FSH-induced mouse oocyte maturation via NOX-ROS-TACE cascade signaling pathway.PloS one · 2014Article
- Brain angiotensin-converting enzyme type 2 shedding contributes to the development of neurogenic hypertension.Circulation research · 2013Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Epidermal growth factor receptor (EGFR) activation by GPCRs regulates many important biological processes. ADAM metalloprotease activity has been implicated as a key step in transactivation, yet the regulatory mechanisms are not fully understood. Here, we investigate the regulation of transforming growth factor-alpha (TGF-alpha) shedding by reactive oxygen species (ROS) through the ATP-dependent activation of the P2Y family of GPCRs. We report that ATP stimulates TGF-alpha proteolysis with concomitant EGFR activation and that this process requires TACE/ADAM17 activity in both murine fibroblasts and CHO cells. ATP-induced TGF-alpha shedding required calcium and was independent of Src family kinases and PKC and MAPK signaling. Moreover, ATP-induced TGF-alpha shedding was completely inhibited by scavengers of ROS, whereas calcium-stimulated shedding was partially inhibited by ROS scavenging. Hydrogen peroxide restored TGF-alpha shedding after calcium chelation. Importantly, we also found that ATP-induced shedding was independent of the cytoplasmic NADPH oxidase complex. Instead, mitochondrial ROS production increased in response to ATP and mitochondrial oxidative complex activity was required to activate TACE-dependent shedding. These results reveal an essential role for mitochondrial ROS in regulating GPCR-induced growth factor shedding.
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