ArticleProceedings of the National Academy of Sciences of the United States of America2020
Two-step release of kinase autoinhibition in discoidin domain receptor 1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Targeted DDR1 Treatment Strategy Enhances PD-1 Immunotherapy Efficacy against Gastric Cancer.Journal of medicinal chemistry · 2025Article
- The use of intuitive AF-based modelling for the understanding of activation and signalling through insulin-like receptors.Frontiers in endocrinology · 2025Review
- Warburg-Cinotti disease variant p.Tyr740Cys enhances catalytic activity of DDR2 kinase.PloS one · 2025Article
- Structure of LRRK1 and mechanisms of autoinhibition and activation.Nature structural & molecular biology · 2023Article
- LIMS-Kinase provides sensitive and generalizable label-freeCell reports. Physical science · 2023Article
- Extracellular matrix-induced signaling pathways in mesenchymal stem/stromal cells.Cell communication and signaling : CCS · 2023Review
- Genetic and pharmacological tools to study the role of discoidin domain receptors in kidney disease.Frontiers in pharmacology · 2022Review
- Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation.Biomolecules · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase with important functions in organogenesis and tissue homeostasis. Aberrant DDR1 activity contributes to the progression of human diseases, including fibrosis and cancer. How DDR1 activity is regulated is poorly understood. We investigated the function of the long intracellular juxtamembrane (JM) region of human DDR1 and found that the kinase-proximal segment, JM4, is an important regulator of kinase activity. Crystal structure analysis revealed that JM4 forms a hairpin that penetrates the kinase active site, reinforcing autoinhibition by the activation loop. Using in vitro enzymology with soluble kinase constructs, we established that release from autoinhibition occurs in two distinct steps: rapid autophosphorylation of the JM4 tyrosines, Tyr569 and Tyr586, followed by slower autophosphorylation of activation loop tyrosines. Mutation of JM4 tyrosines abolished collagen-induced DDR1 activation in cells. The insights may be used to develop allosteric, DDR1-specific, kinase inhibitors.
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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.