ArticleThe Journal of biological chemistry2015
The cytoplasmic domain of a disintegrin and metalloproteinase 10 (ADAM10) regulates its constitutive activity but is dispensable for stimulated ADAM10-dependent shedding.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- ADAM Proteases in Cancer: Biological Roles, Therapeutic Challenges, and Emerging Opportunities.Cancers · 2025Review
- A Valuable Target for Therapy: The Metalloproteinase ADAM10.Current protein & peptide science · 2025Review
- Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes.Cell communication and signaling : CCS · 2024Article
- Alpha-lipoic acid alleviates cognitive deficits in transgenic APP23/PS45 mice through a mitophagy-mediated increase in ADAM10 α-secretase cleavage of APP.Alzheimer's research & therapy · 2024Article
- A Disintegrin and metalloproteinase carves T cell abnormalities and pathogenesis in systemic lupus erythematosus.Clinical immunology (Orlando, Fla.) · 2024Review
- ADAM10-a "multitasker" in sepsis: focus on its posttranslational target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- A Bioengineering Strategy to Control ADAM10 Activity in Living Cells.International journal of molecular sciences · 2023Article
- The versatile roles of ADAM8 in cancer cell migration, mechanics, and extracellular matrix remodeling.Frontiers in cell and developmental biology · 2023Review
- Scramblases as Regulators of ProteolyticMembranes · 2022Review
- ADAM10-Mediated Ectodomain Shedding Is an Essential Driver of Podocyte Damage.Journal of the American Society of Nephrology : JASN · 2021Article
- ADAM10 Site-Dependent Biology: Keeping Control of a Pervasive Protease.International journal of molecular sciences · 2021Review
- Members of the Fibroblast Growth Factor Receptor Superfamily Are Proteolytically Cleaved by Two Differently Activated Metalloproteases.International journal of molecular sciences · 2021Article
- Analysis of the Conditions That Affect the Selective Processing of Endogenous Notch1 by ADAM10 and ADAM17.International journal of molecular sciences · 2021Article
- Article
- Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells.eLife · 2020Article
- ADAM10 sheddase activation is controlled by cell membrane asymmetry.Journal of molecular cell biology · 2019Article
- Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous system.Cellular and molecular life sciences : CMLS · 2019Review
- Scissor sisters: regulation of ADAM10 by the TspanC8 tetraspanins.Biochemical Society transactions · 2017Review
- Regulation of A disintegrin and metalloproteinase (ADAM) family sheddases ADAM10 and ADAM17: The emerging role of tetraspanins and rhomboids.Platelets · 2017Review
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
The membrane-anchored metalloproteinase a disintegrin and metalloprotease 10 (ADAM10) is required for shedding of membrane proteins such as EGF, betacellulin, the amyloid precursor protein, and CD23 from cells. ADAM10 is constitutively active and can be rapidly and post-translationally enhanced by several stimuli, yet little is known about the underlying mechanism. Here, we use ADAM10-deficient cells transfected with wild type or mutant ADAM10 to address the role of its cytoplasmic and transmembrane domain in regulating ADAM10-dependent protein ectodomain shedding. We report that the cytoplasmic domain of ADAM10 negatively regulates its constitutive activity through an ER retention motif but is dispensable for its stimulated activity. However, chimeras with the extracellular domain of ADAM10 and the transmembrane domain of ADAM17 with or without the cytoplasmic domain of ADAM17 show reduced stimulated shedding of the ADAM10 substrate betacellulin, whereas the ionomycin-stimulated shedding of the ADAM17 substrates CD62-L and TGFα is not affected. Moreover, we show that influx of extracellular calcium activates ADAM10 but is not essential for its activation by APMA and BzATP. Finally, the rapid stimulation of ADAM10 is not significantly affected by incubation with proprotein convertase inhibitors for up to 8 h, arguing against a major role of increased prodomain removal in the rapid stimulation of ADAM10. Thus, the cytoplasmic domain of ADAM10 negatively influences constitutive shedding through an ER retention motif, whereas the cytoplasmic domain and prodomain processing are not required for the rapid activation of ADAM10-dependent shedding events.
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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.