ArticleProceedings of the National Academy of Sciences of the United States of America2013
Regulated ADAM17-dependent EGF family ligand release by substrate-selecting signaling pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 86 citations in OpenAlex.
- ErbB signaling in brain injury regeneration: Pathway interactions and therapeutic potential.Neural regeneration research · 2026Article
- IL-17RA signaling promotes the dedifferentiation of Paneth progenitors through ADAM17 to regenerate gut epithelium post-irradiation.Nature communications · 2026Article
- The ADAM Family of Proteases: Structure, Substrates, and Roles in Liver Diseases.International journal of molecular sciences · 2026Review
- The subventricular zone neurogenic niche provides adult born functional neurons to repair cortical brain injuries in response to diterpenoid therapy.Stem cell research & therapy · 2025Article
- Low-affinity ligands of the epidermal growth factor receptor are long-range signal transmitters in collective cell migration of epithelial cells.Cell reports · 2024Article
- Targeting epidermal growth factor receptor to recruit newly generated neuroblasts in cortical brain injuries.Journal of translational medicine · 2023Article
- Rescue of neurogenesis and age-associated cognitive decline in SAMP8 mouse: Role of transforming growth factor-alpha.Aging cell · 2023Article
- PPP1R14D promotes the proliferation, migration and invasion of lung adenocarcinoma via the PKCα/BRAF/MEK/ERK signaling pathway.International journal of oncology · 2022Article
- MAGI-1 PDZ2 Domain Blockade Averts Adenovirus Infection via Enhanced Proteolysis of the Apical Coxsackievirus and Adenovirus Receptor.Journal of virology · 2021Article
- Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- Targeting Protein Kinase C in Glioblastoma Treatment.Biomedicines · 2021Review
- Suppression of α-catenin and adherens junctions enhances epithelial cell proliferation and motility via TACE-mediated TGF-α autocrine/paracrine signaling.Molecular biology of the cell · 2021Article
- ADAM17-triggered TNF signalling protects the ageing Drosophila retina from lipid droplet-mediated degeneration.The EMBO journal · 2020Article
- Neuregulin 1: an intriguing therapeutic target for neurodevelopmental disorders.Translational psychiatry · 2020Review
- A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries.Cell death & disease · 2020Article
- ADAM17: An Emerging Therapeutic Target for Lung Cancer.Cancers · 2019Review
- ADAM17/TACE: a key molecule in brain injury regeneration.Neural regeneration research · 2019Article
- Protein Kinase C: Targets to Regenerate Brain Injuries?Frontiers in cell and developmental biology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Ectodomain cleavage of cell-surface proteins by A disintegrin and metalloproteinases (ADAMs) is highly regulated, and its dysregulation has been linked to many diseases. ADAM10 and ADAM17 cleave most disease-relevant substrates. Broad-spectrum metalloprotease inhibitors have failed clinically, and targeting the cleavage of a specific substrate has remained impossible. It is therefore necessary to identify signaling intermediates that determine substrate specificity of cleavage. We show here that phorbol ester or angiotensin II-induced proteolytic release of EGF family members may not require a significant increase in ADAM17 protease activity. Rather, inducers activate a signaling pathway using PKC-α and the PKC-regulated protein phosphatase 1 inhibitor 14D that is required for ADAM17 cleavage of TGF-α, heparin-binding EGF, and amphiregulin. A second pathway involving PKC-δ is required for neuregulin (NRG) cleavage, and, indeed, PKC-δ phosphorylation of serine 286 in the NRG cytosolic domain is essential for induced NRG cleavage. Thus, signaling-mediated substrate selection is clearly distinct from regulation of enzyme activity, an important mechanism that offers itself for application in disease.
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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.