ArticleMolecular and cellular biology2015
Distinct Intracellular Domain Substrate Modifications Selectively Regulate Ectodomain Cleavage of NRG1 or CD44.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- CD44 Intracellular Domain: A Long Tale of a Short Tail.Cancers · 2023Review
- The potential role of interleukin (IL)-25/IL-33/thymic stromal lymphopoietin (TSLP) on the pathogenesis of idiopathic pulmonary fibrosis.The clinical respiratory journal · 2022Review
- Immunomodulatory role of metalloproteinase ADAM17 in tumor development.Frontiers in immunology · 2022Review
- Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies.Science advances · 2021Article
- Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts.Oncogene · 2021Article
- The Tumor Proteolytic Landscape: A Challenging Frontier in Cancer Diagnosis and Therapy.International journal of molecular sciences · 2021Review
- ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc.Cancer cell international · 2021Article
- Integrated analysis of Shank1 PDZ interactions with C-terminal and internal binding motifs.Current research in structural biology · 2021Article
- iRhom2: An Emerging Adaptor Regulating Immunity and Disease.International journal of molecular sciences · 2020Review
- Neuregulin 1: an intriguing therapeutic target for neurodevelopmental disorders.Translational psychiatry · 2020Review
- RIP at the Synapse and the Role of Intracellular Domains in Neurons.Neuromolecular medicine · 2020Review
- NMDA Receptors Regulate Neuregulin 2 Binding to ER-PM Junctions and Ectodomain Release by ADAM10 [corrected].Molecular neurobiology · 2019Article
- Article
- L1cam-mediated developmental processes of the nervous system are differentially regulated by proteolytic processing.Scientific reports · 2019Article
- Nrg1 Intracellular Signaling Is Neuroprotective upon Stroke.Oxidative medicine and cellular longevity · 2019Article
- MMP-13 binds to platelet receptors αIIbβ3 and GPVI and impairs aggregation and thrombus formation.Research and practice in thrombosis and haemostasis · 2018Article
- Functional Genomics Approach Identifies Novel Signaling Regulators of TGFα Ectodomain Shedding.Molecular cancer research : MCR · 2018Article
- Gamma secretase dependent release of the CD44 cytoplasmic tail upregulates IFI16 in cd44-/- tumor cells, MEFs and macrophages.PloS one · 2018Article
- Scissor sisters: regulation of ADAM10 by the TspanC8 tetraspanins.Biochemical Society transactions · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Ectodomain cleavage by A-disintegrin and -metalloproteases (ADAMs) releases many important biologically active substrates and is therefore tightly controlled. Part of the regulation occurs on the level of the enzymes and affects their cell surface abundance and catalytic activity. ADAM-dependent proteolysis occurs outside the plasma membrane but is mostly controlled by intracellular signals. However, the intracellular domains (ICDs) of ADAM10 and -17 can be removed without consequences for induced cleavage, and so far it is unclear how intracellular signals address cleavage. We therefore explored whether substrates themselves could be chosen for proteolysis via ICD modification. We report here that CD44 (ADAM10 substrate), a receptor tyrosine kinase (RTK) coreceptor required for cellular migration, and pro-NRG1 (ADAM17 substrate), which releases the epidermal growth factor (EGF) ligand neuregulin required for axonal outgrowth and myelination, are indeed posttranslationally modified at their ICDs. Tetradecanoyl phorbol acetate (TPA)-induced CD44 cleavage requires dephosphorylation of ICD serine 291, while induced neuregulin release depends on the phosphorylation of several NRG1-ICD serines, in part mediated by protein kinase Cδ (PKCδ). Downregulation of PKCδ inhibits neuregulin release and reduces ex vivo neurite outgrowth and myelination of trigeminal ganglion explants. Our results suggest that specific selection among numerous substrates of a given ADAM is determined by ICD modification of the substrate.
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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.