ArticleCell reports2017
Phosphorylation of iRhom2 Controls Stimulated Proteolytic Shedding by the Metalloprotease ADAM17/TACE.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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Who cites it
60 citing papers in PubMed, 116 citations in OpenAlex.
- Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease.Nature immunology · 2022Trial
- ADAM17 and its proteolytic targets in disease pathogenesis.The FEBS journal · 2026Review
- Transferrin receptor 1 shedding by the pro-inflammatory iRhom-ADAM17 complex and ADAM10 regulates cellular iron uptake and ferroptosis.Experimental & molecular medicine · 2026Article
- Structural basis for ADAM17 activation by the iRhom1 pseudoprotease.Cell reports · 2026Article
- ADAM17 as a proteolytic rheostat linking inflammation, tissue repair, and failure of inflammatory resolution in liver injury and fibrosis.Frontiers in pharmacology · 2026Review
- Structural insights into the activation and inhibition of the ADAM17-iRhom2 complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Progress of ADAM17 in Fibrosis-Related Diseases.Mediators of inflammation · 2025Review
- Review
- Angiotensin-Converting Enzyme 2 Posttranslational Modifications and Implications for Hypertension and SARS-CoV-2: 2023 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Cryo-EM reveals that iRhom2 restrains ADAM17 protease activity to control the release of growth factor and inflammatory signals.Molecular cell · 2024Article
- Role of iRhom2 in Olfaction: Implications for Odorant Receptor Regulation and Activity-Dependent Adaptation.International journal of molecular sciences · 2024Article
- Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.Cellular and molecular life sciences : CMLS · 2024Article
- Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy.Nature communications · 2024Article
- Breakdown of Phospholipid Asymmetry Triggers ADAM17-Mediated Rescue Events in Cells Undergoing Apoptosis.Membranes · 2023Article
- Systematic analysis of the Frazzled receptor interactome establishes previously unreported regulators of axon guidance.Development (Cambridge, England) · 2023Article
- A structural model of the iRhom-ADAM17 sheddase complex reveals functional insights into its trafficking and activity.Cellular and molecular life sciences : CMLS · 2023Article
- The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth.Life science alliance · 2023Article
- Identification of Molecular Determinants in iRhoms1 and 2 That Contribute to the Substrate Selectivity of Stimulated ADAM17.International journal of molecular sciences · 2022Article
- ADAM17 cleaves the insulin receptor ectodomain on endothelial cells and causes vascular insulin resistance.American journal of physiology. Heart and circulatory physiology · 2022Article
- iRhom2 regulates ERBB signalling to promote KRAS-driven tumour growth of lung cancer cells.Journal of cell science · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Cell surface metalloproteases coordinate signaling during development, tissue homeostasis, and disease. TACE (TNF-α-converting enzyme), is responsible for cleavage ("shedding") of membrane-tethered signaling molecules, including the cytokine TNF, and activating ligands of the EGFR. The trafficking of TACE within the secretory pathway requires its binding to iRhom2, which mediates the exit of TACE from the endoplasmic reticulum. An important, but mechanistically unclear, feature of TACE biology is its ability to be stimulated rapidly on the cell surface by numerous inflammatory and growth-promoting agents. Here, we report a role for iRhom2 in TACE stimulation on the cell surface. TACE shedding stimuli trigger MAP kinase-dependent phosphorylation of iRhom2 N-terminal cytoplasmic tail. This recruits 14-3-3 proteins, enforcing the dissociation of TACE from complexes with iRhom2, promoting the cleavage of TACE substrates. Our data reveal that iRhom2 controls multiple aspects of TACE biology, including stimulated shedding on the cell surface.
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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.