ArticleThe Journal of biological chemistry2014
Normal activation of discoidin domain receptor 1 mutants with disulfide cross-links, insertions, or deletions in the extracellular juxtamembrane region: mechanistic implications.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Transmembrane association of DDR1 and DDR2 mediated by Leucine zipper motifs.Magnetic resonance letters · 2025Article
- Warburg-Cinotti disease variant p.Tyr740Cys enhances catalytic activity of DDR2 kinase.PloS one · 2025Article
- Discoid Domain Receptors Signaling in Macrophages-Mediated Diseases.International journal of general medicine · 2025Review
- Focusing on discoidin domain receptors in premalignant and malignant liver diseases.Frontiers in oncology · 2023Review
- Two-step release of kinase autoinhibition in discoidin domain receptor 1.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Chain alignment of collagen I deciphered using computationally designed heterotrimers.Nature chemical biology · 2020Article
- Transmembrane Peptides as Inhibitors of Protein-Protein Interactions: An Efficient Strategy to Target Cancer Cells?Frontiers in oncology · 2020Review
- DDR1 autophosphorylation is a result of aggregation into dense clusters.Scientific reports · 2019Article
- Discoidin domain receptors: Micro insights into macro assemblies.Biochimica et biophysica acta. Molecular cell research · 2019Review
- Cell-based Assay for Recruitment of DDR1 to Collagen-coated Beads.Bio-protocol · 2019Article
- Clustering, Spatial Distribution, and Phosphorylation of Discoidin Domain Receptors 1 and 2 in Response to Soluble Collagen I.Journal of molecular biology · 2019Article
- Multitasking discoidin domain receptors are involved in several and specific hallmarks of cancer.Cell adhesion & migration · 2018Review
- Mechanical signaling through the discoidin domain receptor 1 plays a central role in tissue fibrosis.Cell adhesion & migration · 2018Review
- Collagen induces activation of DDR1 through lateral dimer association and phosphorylation between dimers.eLife · 2017Article
- Clustering of glycoprotein VI (GPVI) dimers upon adhesion to collagen as a mechanism to regulate GPVI signaling in platelets.Journal of thrombosis and haemostasis : JTH · 2017Article
- Novel cross talk between IGF-IR and DDR1 regulates IGF-IR trafficking, signaling and biological responses.Oncotarget · 2015Article
- Discoidin domain receptor 1 (DDR1) kinase as target for structure-based drug discovery.Drug discovery today · 2015Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The discoidin domain receptors, DDR1 and DDR2, are receptor tyrosine kinases that are activated by collagen. DDR activation does not appear to occur by the common mechanism of ligand-induced receptor dimerization: the DDRs form stable noncovalent dimers in the absence of ligand, and ligand-induced autophosphorylation of cytoplasmic tyrosines is unusually slow and sustained. Here we sought to identify functionally important dimer contacts within the extracellular region of DDR1 by using cysteine-scanning mutagenesis. Cysteine substitutions close to the transmembrane domain resulted in receptors that formed covalent dimers with high efficiency, both in the absence and presence of collagen. Enforced covalent dimerization did not result in constitutive activation and did not affect the ability of collagen to induce receptor autophosphorylation. Cysteines farther away from the transmembrane domain were also cross-linked with high efficiency, but some of these mutants could no longer be activated. Furthermore, the extracellular juxtamembrane region of DDR1 tolerated large deletions as well as insertions of flexible segments, with no adverse effect on activation. These findings indicate that the extracellular juxtamembrane region of DDR1 is exceptionally flexible and does not constrain the basal or ligand-activated state of the receptor. DDR1 transmembrane signaling thus appears to occur without conformational coupling through the juxtamembrane region, but requires specific receptor interactions farther away from the cell membrane. A plausible mechanism to explain these findings is signaling by DDR1 clusters.
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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.