ArticleThe Journal of cell biology2007
DSL ligand endocytosis physically dissociates Notch1 heterodimers before activating proteolysis can occur.
Article in The Journal of cell biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
What it found
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Who cites it
126 citing papers in PubMed, 249 citations in OpenAlex.
- SynNotch Receptors for Visualizing Immunoreceptor Force Transmission and Downstream Signaling In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SynNotch receptors for visualizing immunoreceptor force transmission and downstream signaling in vivo.bioRxiv : the preprint server for biology · 2026Article
- Monocyte Dll4 Contributes to Systemic Inflammation in People Living With HIV.Circulation research · 2026Article
- Interleukin-7 induces EMT to promote tumor growth and metastasis in NSCLC via Notch1/TGF-β pathway.Scientific reports · 2026Article
- The Notch signaling pathway in regulating bone and cartilage homeostasis: novel insights into the pathogenesis and therapeutics of osteoarthritis.Cell communication and signaling : CCS · 2025Review
- Cholesterol metabolism on stem cell fate determination: a frontier horizon.Stem cell research & therapy · 2025Review
- Signaling pathways and molecular mechanisms involved in the onset and progression of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); a focus on Notch3 signaling.The journal of headache and pain · 2025Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Synergistic effects of mutation and glycosylation on disease progression.Frontiers in molecular biosciences · 2025Review
- The N-acetylglucosaminyltransferase Radical fringe contributes to defects in JAG1-dependent turnover and signaling of NOTCH3 CADASIL mutants.The Journal of biological chemistry · 2024Article
- Temporal dynamics and stoichiometry in human Notch signaling from Notch synaptic complex formation to nuclear entry of the Notch intracellular domain.Developmental cell · 2024Article
- Regulation of Notch signaling by non-muscle myosin II Zipper in Drosophila.Cellular and molecular life sciences : CMLS · 2024Article
- Progress to Clarify HowBiomolecules · 2024Review
- Toll-like receptors as a missing link in Notch signaling cascade during neurodevelopment.Frontiers in molecular neuroscience · 2024Article
- New mutant alleles for Spargel/dPGC-1 highlights the function of Spargel RRM domain in oogenesis and expands the role of Spargel in embryogenesis and intracellular transport.G3 (Bethesda, Md.) · 2023Article
- Functional Comparison between Endogenous and Synthetic Notch Systems.ACS synthetic biology · 2022Article
- Intrinsically disordered protein regions are required for cell wall homeostasis inGenes & development · 2022Article
- Article
- NOTCH1 Signalling: A key pathway for the development of high-risk chronic lymphocytic leukaemia.Frontiers in oncology · 2022Review
- The Role of Intracellular Trafficking of Notch Receptors in Ligand-Independent Notch Activation.Biomolecules · 2021Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Cleavage of Notch by furin is required to generate a mature, cell surface heterodimeric receptor that can be proteolytically activated to release its intracellular domain, which functions in signal transduction. Current models propose that ligand binding to heterodimeric Notch (hNotch) induces a disintegrin and metalloprotease (ADAM) proteolytic release of the Notch extracellular domain (NECD), which is subsequently shed and/or endocytosed by DSL ligand cells. We provide evidence for NECD release and internalization by DSL ligand cells, which, surprisingly, did not require ADAM activity. However, losses in either hNotch formation or ligand endocytosis significantly decreased NECD transfer to DSL ligand cells, as well as signaling in Notch cells. Because endocytosis-defective ligands bind hNotch, but do not dissociate it, additional forces beyond those produced through ligand binding must function to disrupt the intramolecular interactions that keep hNotch intact and inactive. Based on our findings, we propose that mechanical forces generated during DSL ligand endocytosis function to physically dissociate hNotch, and that dissociation is a necessary step in Notch activation.
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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.