ArticleThe Biochemical journal2013
Phosphoproteomics of collagen receptor networks reveals SHP-2 phosphorylation downstream of wild-type DDR2 and its lung cancer mutants.
Article in The Biochemical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 75 citations in OpenAlex.
- Potentially functional variants of PARK7 and DDR2 in ferroptosis-related genes predict survival of non-small cell lung cancer patients.International journal of cancer · 2025Article
- Synergistic Inhibition of Drug Resistant KRAS Mutant Non-Small Cell Lung Cancer by Co-Targeting AXL and SRC.Cancers · 2025Article
- Warburg-Cinotti disease variant p.Tyr740Cys enhances catalytic activity of DDR2 kinase.PloS one · 2025Article
- Label-Free SERS Sensors for Real-Time Monitoring of Tyrosine Phosphorylation.Analytical chemistry · 2024Article
- Discoidin domain receptor 2 signaling through PIK3C2α in fibroblasts promotes lung fibrosis.The Journal of pathology · 2024Article
- LIMS-Kinase provides sensitive and generalizable label-freeCell reports. Physical science · 2023Article
- From Stem to Sternum: The Role of Shp2 in the Skeleton.Calcified tissue international · 2023Review
- Focusing on discoidin domain receptors in premalignant and malignant liver diseases.Frontiers in oncology · 2023Review
- Genetic and pharmacological tools to study the role of discoidin domain receptors in kidney disease.Frontiers in pharmacology · 2022Review
- COL10A1-DDR2 axis promotes the progression of pancreatic cancer by regulating MEK/ERK signal transduction.Frontiers in oncology · 2022Article
- The collagen structure of C1q induces wound healing by engaging discoidin domain receptor 2.Molecular medicine (Cambridge, Mass.) · 2021Article
- Tyrosine kinase-independent actions of DDR2 in tumor cells and cancer-associated fibroblasts influence tumor invasion, migration and metastasis.Journal of cell science · 2021Article
- Complex roles of discoidin domain receptor tyrosine kinases in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- The Extracellular Matrix in Soft Tissue Sarcomas: Pathobiology and Cellular Signalling.Frontiers in cell and developmental biology · 2021Review
- 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
- Discoidin Domain Receptors, DDR1b and DDR2, Promote Tumour Growth within Collagen but DDR1b Suppresses Experimental Lung Metastasis in HT1080 Xenografts.Scientific reports · 2020Article
- The role of collagen in cancer: from bench to bedside.Journal of translational medicine · 2019Review
- DDR1 and MT1-MMP Expression Levels Are Determinant for Triggering BIK-Mediated Apoptosis by 3D Type I Collagen Matrix in Invasive Basal-Like Breast Carcinoma Cells.Frontiers in pharmacology · 2019Article
- Biopolymer nanofibrils: structure, modeling, preparation, and applications.Progress in polymer science · 2018Article
- Spatial localisation of Discoidin Domain Receptor 2 (DDR2) signalling is dependent on its collagen binding and kinase activity.Biochemical and biophysical research communications · 2018Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Collagen is an important extracellular matrix component that directs many fundamental cellular processes including differentiation, proliferation and motility. The signalling networks driving these processes are propagated by collagen receptors such as the β1 integrins and the DDRs (discoidin domain receptors). To gain an insight into the molecular mechanisms of collagen receptor signalling, we have performed a quantitative analysis of the phosphorylation networks downstream of collagen activation of integrins and DDR2. Temporal analysis over seven time points identified 424 phosphorylated proteins. Distinct DDR2 tyrosine phosphorylation sites displayed unique temporal activation profiles in agreement with in vitro kinase data. Multiple clustering analysis of the phosphoproteomic data revealed several DDR2 candidate downstream signalling nodes, including SHP-2 (Src homology 2 domain-containing protein tyrosine phosphatase 2), NCK1 (non-catalytic region of tyrosine kinase adaptor protein 1), LYN, SHIP-2 [SH2 (Src homology 2)-domain-containing inositol phosphatase 2], PIK3C2A (phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2α) and PLCL2 (phospholipase C-like 2). Biochemical validation showed that SHP-2 tyrosine phosphorylation is dependent on DDR2 kinase activity. Targeted proteomic profiling of a panel of lung SCC (squamous cell carcinoma) DDR2 mutants demonstrated that SHP-2 is tyrosine-phosphorylated by the L63V and G505S mutants. In contrast, the I638F kinase domain mutant exhibited diminished DDR2 and SHP-2 tyrosine phosphorylation levels which have an inverse relationship with clonogenic potential. Taken together, the results of the present study indicate that SHP-2 is a key signalling node downstream of the DDR2 receptor which may have therapeutic implications in a subset of DDR2 mutations recently uncovered in genome-wide lung SCC sequencing screens.
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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.