ArticleNature communications2015
The sorting protein PACS-2 promotes ErbB signalling by regulating recycling of the metalloproteinase ADAM17.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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
30 citing papers in PubMed, 52 citations in OpenAlex.
- PACS2 at Mitochondria-Associated Membranes: A Central Regulator of Cardiovascular and Metabolic Diseases.Journal of cellular and molecular medicine · 2026Review
- Review
- Understanding PACS2 syndrome's pathomechanism by studying E209K and E211K mutations.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- PACS deficiency disrupts Golgi architecture and causes cytokinesis failures and seizure-like phenotype inOpen biology · 2025Article
- The PACS-2 protein and trafficking motifs in CCHFV Gn and Gc cytoplasmic domains govern CCHFV assembly.Emerging microbes & infections · 2024Article
- Role of Metalloproteinases in Diabetes-associated Mild Cognitive Impairment.Current neuropharmacology · 2024Review
- Mitochondria-associated membrane protein PACS2 maintains right cardiac function in hypobaric hypoxia.iScience · 2023Article
- The Phosphofurin Acidic Cluster Sorting Protein 2 (PACS-2) E209K Mutation Responsible for PACS-2 Syndrome Increases Susceptibility to Apoptosis.ACS omega · 2022Article
- Downregulation of ADAM17 in pediatric immune thrombocytopenia impairs proplatelet formation.BMC pediatrics · 2022Article
- Shikonin suppresses colon cancer cell growth and exerts synergistic effects by regulating ADAM17 and the IL‑6/STAT3 signaling pathway.International journal of oncology · 2021Article
- Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- ADAM17 is an essential attachment factor for classical swine fever virus.PLoS pathogens · 2021Article
- Comprehensive Analysis of the Effects of Genetic Ancestry and Genetic Characteristics on the Clinical Evolution of Oral Squamous Cell Carcinoma.Frontiers in cell and developmental biology · 2021Article
- Impairment of carbonic anhydrase IX ectodomain cleavage reinforces tumorigenic and metastatic phenotype of cancer cells.British journal of cancer · 2020Article
- Differential Induction of the ADAM17 Regulators iRhom1 and 2 in Endothelial Cells.Frontiers in cardiovascular medicine · 2020Article
- Review
- PACS-2 functions in colorectal cancer.Aging · 2018Article
- iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE.eLife · 2018Article
- Sorting nexin 9 (SNX9) regulates levels of the transmembrane ADAM9 at the cell surface.The Journal of biological chemistry · 2018Article
- ADAM17 inhibition enhances platinum efficiency in ovarian cancer.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
The metalloproteinase ADAM17 activates ErbB signalling by releasing ligands from the cell surface, a key step underlying epithelial development, growth and tumour progression. However, mechanisms acutely controlling ADAM17 cell-surface availability to modulate the extent of ErbB ligand release are poorly understood. Here, through a functional genome-wide siRNA screen, we identify the sorting protein PACS-2 as a regulator of ADAM17 trafficking and ErbB signalling. PACS-2 loss reduces ADAM17 cell-surface levels and ADAM17-dependent ErbB ligand shedding, without apparent effects on related proteases. PACS-2 co-localizes with ADAM17 on early endosomes and PACS-2 knockdown decreases the recycling and stability of internalized ADAM17. Hence, PACS-2 sustains ADAM17 cell-surface activity by diverting ADAM17 away from degradative pathways. Interestingly, Pacs2-deficient mice display significantly reduced levels of phosphorylated EGFR and intestinal proliferation. We suggest that this mechanism controlling ADAM17 cell-surface availability and EGFR signalling may play a role in intestinal homeostasis, with potential implications for cancer biology.
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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.