ArticleMolecular biology of the cell2017
Genome-wide screen of gamma-secretase-mediated intramembrane cleavage of receptor tyrosine kinases.
Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- N-Glycosylation of AXL Receptor Tyrosine Kinase Regulates Its Stability, Phosphorylation, and Oncogenic Function.Molecular & cellular proteomics : MCP · 2026Article
- Multiple glycoforms of TrkA interact with N-cadherin during trigeminal ganglion neurodevelopment.Journal of cell science · 2026Article
- Sublytic pyroptosis blocks Schwann cell remyelination through caspase-1-mediated Tyro3 cleavage.Journal of neuroinflammation · 2026Article
- Ferroptosis-Related Diagnostic Biomarkers in Diabetic Kidney Disease: A Multi-Omics and Multi-Cohort Study.Journal of inflammation research · 2026Article
- Shedding Phosphorylated Axl Receptor in Lung Adenocarcinoma: Dual-Domain Immunohistochemistry Approach.JTO clinical and research reports · 2025Article
- Charting γ-secretase substrates by explainable AI.Nature communications · 2025Article
- Proteolysis of TAM receptors in autoimmune diseases and cancer: what does it say to us?Cell death & disease · 2025Review
- Article
- The manipulator behind "Scissors": γ -secretase and its modulators in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Role and Mechanisms of Tyro3 in Podocyte Biology and Glomerular Disease.Kidney diseases (Basel, Switzerland) · 2024Review
- Hallmarks of pancreatic cancer: spotlight on TAM receptors.EBioMedicine · 2024Review
- A Non-Canonical p75HER2 Signaling Pathway Underlying Trastuzumab Action and Resistance in Breast Cancer.Cells · 2024Article
- Trans-activating mutations of the pseudokinase ERBB3.Oncogene · 2024Article
- Alzheimer's disease-associated P460L variant of EphA1 dysregulates receptor activity and blood-brain barrier function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Peptidoglycan from Bacillus anthracis Inhibits Human Macrophage Efferocytosis in Part by Reducing Cell Surface Expression of MERTK and TIM-3.ImmunoHorizons · 2024Article
- TAM family kinases as therapeutic targets at the interface of cancer and immunity.Nature reviews. Clinical oncology · 2023Review
- Article
- An extracellular receptor tyrosine kinase motif orchestrating intracellular STAT activation.Nature communications · 2022Article
- Identification of in vivo roles of ErbB4-JMa and its direct nuclear signaling using a novel isoform-specific knock out mouse.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Receptor tyrosine kinases (RTKs) have been demonstrated to signal via regulated intramembrane proteolysis, in which ectodomain shedding and subsequent intramembrane cleavage by gamma-secretase leads to release of a soluble intracellular receptor fragment with functional activity. For most RTKs, however, it is unknown whether they can exploit this new signaling mechanism. Here we used a system-wide screen to address the frequency of susceptibility to gamma-secretase cleavage among human RTKs. The screen covering 45 of the 55 human RTKs identified 12 new as well as all nine previously published gamma-secretase substrates. We biochemically validated the screen by demonstrating that the release of a soluble intracellular fragment from endogenous AXL was dependent on the sheddase disintegrin and metalloprotease 10 (ADAM10) and the gamma-secretase component presenilin-1. Functional analysis of the cleavable RTKs indicated that proliferation promoted by overexpression of the TAM family members AXL or TYRO3 depends on gamma-secretase cleavage. Taken together, these data indicate that gamma-secretase-mediated cleavage provides an additional signaling mechanism for numerous human RTKs.
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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.