Affinage

DDR2

Discoidin domain-containing receptor 2 · UniProt Q16832

Round 2 corrected
Length
855 aa
Mass
96.7 kDa
Annotated
2026-04-28
130 papers in source corpus 54 papers cited in narrative 54 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDR2 is a collagen-activated receptor tyrosine kinase that transduces extracellular matrix signals into programs governing cell proliferation, differentiation, ECM remodeling, epithelial-mesenchymal transition, and immune evasion. Native triple-helical collagens (types I, II, III, X) bind the DDR2 discoidin domain—specifically recognizing the GVMGFO motif via an amphiphilic pocket formed by three surface loops—triggering slow autophosphorylation (including Y740) that requires Src for maximal activation, with downstream signaling proceeding through Src-Shc, ERK1/2 (which directly phosphorylates and stabilizes SNAIL1 to drive EMT and metastasis), p38 MAPK–Runx2, JAK2, NF-κB, STAT3, YAP/TAZ, and mTOR pathways (PMID:9659899, PMID:11884411, PMID:20004161, PMID:23644467, PMID:20564243). Beyond kinase-dependent signaling, the DDR2 extracellular domain inhibits collagen fibrillogenesis independently of catalytic activity, and DDR2 forms a complex with Nrp1–PlexinA1 to suppress osteoclastogenesis, while in cancer-associated fibroblasts it controls collagen fiber organization, integrin mechanotransduction via Rap1–Talin1–Kindlin2, and metabolic reprogramming through an AKT/SNAI1–glycolysis axis (PMID:18996394, PMID:25805889, PMID:31144616, PMID:37527178). Loss-of-function DDR2 mutations—causing either ER retention of misfolded kinase-domain variants or collagen-binding defects in the discoidin domain—underlie spondylo-meta-epiphyseal dysplasia short limb–hand type (SMED-SL), whereas gain-of-function mutations drive squamous cell lung cancer and Warburg-Cinotti syndrome (PMID:19110212, PMID:20223752, PMID:22328973, PMID:30449416).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 High

    The fundamental question of what activates DDR2 was answered: native triple-helical collagen, not soluble growth factors, triggers DDR2 tyrosine kinase activity and upregulates MMP-1, establishing DDR2 as a collagen receptor that connects ECM composition to cellular gene expression.

    Evidence Receptor-ligand binding and kinase activation assays in cell lines

    PMID:9659899

    Open questions at the time
    • Downstream signaling intermediates uncharacterized
    • Collagen-type specificity undefined
    • Structural basis of collagen recognition unknown
  2. 2001 High

    The physiological requirement for DDR2 kinase activity was established: DDR2 knockout mice exhibit dwarfism from reduced chondrocyte proliferation, and kinase-dead DDR2 fails to rescue fibroblast proliferation defects, demonstrating that DDR2 catalytic activity is essential for skeletal growth.

    Evidence DDR2 knockout mouse phenotyping plus kinase-dead rescue in fibroblasts; corroborated by constitutively active DDR2 driving stellate cell proliferation and MMP-2 upregulation

    PMID:11375938 PMID:11696582

    Open questions at the time
    • No identification of DDR2 substrates or immediate downstream effectors
    • Mechanism of DDR2-dependent chondrocyte proliferation not defined
  3. 2002 High

    The first signaling intermediates downstream of DDR2 were identified: Src kinase is required for maximal DDR2 phosphorylation and associates with DDR2, while the adaptor Shc bridges DDR2 to downstream pathways including MMP-2 transactivation.

    Evidence Co-immunoprecipitation, dominant-negative Src, and MMP-2 promoter reporter assays

    PMID:11884411

    Open questions at the time
    • Whether Src directly phosphorylates DDR2 or acts via intermediates was unclear
    • Full spectrum of DDR2-interacting adaptors unknown
  4. 2003 High

    The collagen-binding determinant was mapped: three surface loops of the discoidin domain form the collagen recognition site, and the GVMGFO motif within triple-helical collagen was later identified as the minimal binding sequence, ultimately resolved at atomic resolution by crystallography.

    Evidence Loop-swap mutagenesis and solid-phase binding (2003); Toolkit peptide screening (2008); X-ray crystal structure of DDR2 DS domain–collagen peptide complex (2009)

    PMID:12611880 PMID:18201965 PMID:20004161

    Open questions at the time
    • How ligand binding in the extracellular domain is transmitted across the membrane to the kinase domain remains structurally unresolved
    • Full-length DDR2 structure unavailable
  5. 2008 High

    A kinase-independent function of DDR2 was discovered: the extracellular domain alone—whether membrane-tethered kinase-dead or as a shed soluble form—inhibits collagen fibrillogenesis, revealing that DDR2 physically modulates ECM architecture independently of catalytic signaling.

    Evidence Kinase-dead DDR2 and soluble ECD expression in osteoblasts with TEM, fluorescence microscopy, and hydroxyproline assays

    PMID:18996394 PMID:19900459

    Open questions at the time
    • Molecular mechanism of fibrillogenesis inhibition (steric blockade vs. active remodeling) not defined
    • In vivo significance of shed DDR2 ECD unknown
  6. 2009 High

    The genetic basis of SMED-SL was established: kinase-domain mutations (T713I, I726R, R752C) cause ER retention and loss of collagen-induced activation, while the E113K extracellular mutation permits normal trafficking but abolishes collagen binding, demonstrating two distinct loss-of-function mechanisms underlying the same skeletal dysplasia.

    Evidence Expression of mutant DDR2 in cell lines with confocal localization, deglycosylation, and collagen activation assays across multiple studies

    PMID:19110212 PMID:20223752 PMID:24725993

    Open questions at the time
    • Whether ER-retained mutants can be pharmacologically rescued is untested
    • Genotype-phenotype severity correlations not established
  7. 2010 High

    DDR2 was positioned as a driver of osteoblast differentiation through two parallel MAPK cascades: ATF4/C/EBPβ transcriptionally upregulates DDR2, which then activates p38 MAPK–Runx2 and ERK–Runx2 to promote osteogenic gene expression.

    Evidence DDR2 promoter analysis, p38/ERK inhibition, Runx2 phosphorylation assays, constitutively active vs. kinase-dead DDR2 in preosteoblasts

    PMID:20564243 PMID:20734453

    Open questions at the time
    • Direct DDR2 substrates linking to p38 vs. ERK activation unidentified
    • Relative contribution of p38 vs. ERK to in vivo bone formation unclear
  8. 2011 High

    DDR2 was identified as an oncogene in squamous cell lung cancer: somatic gain-of-function mutations (L63V, G505S) cause cellular transformation with DDR2 kinase dependency, as shown by selective killing with DDR2 RNAi and dasatinib.

    Evidence Sequencing of lung SCC tumors, RNAi, dasatinib treatment, xenograft tumor models

    PMID:22328973

    Open questions at the time
    • Structural mechanism by which specific mutations activate DDR2 kinase undefined
    • Clinical response to DDR2-targeted therapy not validated in patients
  9. 2013 High

    A central EMT-driving pathway was delineated: DDR2 activates Src-dependent ERK2, which directly phosphorylates SNAIL1 to prevent its ubiquitylation and promote nuclear accumulation, driving breast cancer invasion and metastasis in vivo—a mechanism subsequently confirmed in HCC, thyroid, and other cancers.

    Evidence In vitro ERK2 kinase assays on SNAIL1, ubiquitylation/cycloheximide chase assays, Src inhibition, mouse metastasis models; extended to HCC and thyroid carcinoma

    PMID:23644467 PMID:26362312 PMID:29250189

    Open questions at the time
    • Whether DDR2-ERK2-SNAIL1 operates in normal tissue homeostasis unclear
    • Phosphosite(s) on SNAIL1 mediating stabilization not fully mapped across cancer types
  10. 2013 High

    Quantitative phosphoproteomics expanded the DDR2 signaling network: SHP-2 was identified as a DDR2 kinase-activity-dependent substrate, with NCK1, LYN, SHIP-2, and PIK3C2A as additional signaling nodes, and dasatinib resistance was shown to arise via DDR2 gatekeeper mutations or NF1-loss-driven RAS-ERK bypass.

    Evidence Quantitative mass spectrometry phosphoproteomics across DDR2 mutants; targeted exome sequencing of resistant lines

    PMID:23822953 PMID:24296828

    Open questions at the time
    • Direct vs. indirect phosphorylation of SHP-2 by DDR2 not resolved
    • In vivo relevance of NF1-loss bypass to clinical resistance unknown
  11. 2015 High

    DDR2 was found to suppress osteoclastogenesis through a non-canonical mechanism: it forms a complex with Nrp1 and PlexinA1, blocking PlexinA1–TREM2/DAP12 interaction and osteoclast stimulation, with in vivo rescue of ovariectomy-induced bone loss.

    Evidence Reciprocal Co-IP for DDR2-Nrp1-PlexinA1 complex, RNAi rescue, adenoviral DDR2 delivery in ovariectomized mice

    PMID:25805889

    Open questions at the time
    • Whether DDR2 kinase activity is required for Nrp1-PlexinA1 complex formation unclear
    • Stoichiometry of the ternary complex undefined
  12. 2016 High

    Cell-type-specific genetic deletion revealed dual roles for DDR2 in cancer: in tumor epithelial cells DDR2 drives collective invasion, while in cancer-associated fibroblasts it controls ECM production and collagen fiber alignment, both being required for metastasis.

    Evidence Cell-type-specific DDR2 deletion, tumor organoid invasion assays, second-harmonic generation microscopy, mouse metastasis models

    PMID:27264173

    Open questions at the time
    • Molecular mechanism of DDR2-dependent collective invasion (leader-cell specification?) unresolved
    • Relative contribution of tumor vs. stromal DDR2 to different metastatic steps not quantified
  13. 2018 High

    Gain-of-function DDR2 variants (L610P, Y740C) were shown to cause Warburg-Cinotti syndrome through ligand-independent kinase activation due to reduced autoinhibition, pharmacologically reversible by dasatinib.

    Evidence Phospho-DDR2 analysis in patient-derived fibroblasts with dasatinib treatment

    PMID:30449416

    Open questions at the time
    • Structural basis of reduced autoinhibition not determined
    • Long-term clinical efficacy of dasatinib in Warburg-Cinotti syndrome unknown
  14. 2019 High

    DDR2 was established as a regulator of tumor mechanotransduction and immune evasion: in CAFs it controls integrin activation through Rap1–Talin1–Kindlin2 to set tumor stiffness, while DDR2 depletion in tumors increases CD8+ T cell infiltration and sensitizes to anti-PD-1 therapy.

    Evidence AFM stiffness measurements, Rap1/Talin1/Kindlin2 activation assays in CAFs; in vivo shRNA screen across five tumor types with CyTOF immune profiling and dasatinib + anti-PD-1 combination

    PMID:30801016 PMID:31144616

    Open questions at the time
    • How DDR2 restricts T cell infiltration mechanistically (ECM barrier vs. direct immune signaling) not resolved
    • Rap1 activation mechanism by DDR2 not fully elucidated
  15. 2022 Medium

    DDR2's metabolic and transcriptional control in the stroma was deepened: in ovarian cancer CAFs, DDR2 regulates arginase-1 transcription via SNAI1, controlling polyamine-dependent collagen production, and modulates glycolysis through an AKT/SNAI1 axis to sustain protein secretion including LOXL2.

    Evidence ChIP for SNAI1 at arginase-1 promoter, metabolomics, glycolytic enzyme assays, secretome proteomics with LOXL2 rescue

    PMID:37527178 PMID:37996700

    Open questions at the time
    • Whether DDR2-dependent metabolic reprogramming is collagen-ligand-dependent or constitutive is unclear
    • Generalizability of arginase/polyamine axis beyond ovarian CAFs not tested
  16. 2024 Medium

    A DDR2–STAT3 positive feedback loop was identified in chemoresistant HCC, where STAT3 drives transcription of PD-L1 and CCL20 to recruit immunosuppressive PMN-MDSCs, mechanistically linking DDR2 to adaptive immune evasion in the tumor microenvironment.

    Evidence DDR2/STAT3 knockdown, dual luciferase reporters for PD-L1/CCL20 promoters, MDSC migration assays, in vivo tumor models

    PMID:38969205

    Open questions at the time
    • Whether this DDR2-STAT3 axis operates in non-hepatic cancers untested
    • Direct DDR2 substrate leading to STAT3 phosphorylation unidentified
    • Clinical relevance of DDR2-dependent immune evasion in patients unconfirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions remain: the structural mechanism by which collagen binding in the extracellular discoidin domain is transmitted across the membrane to activate the intracellular kinase; a full-length DDR2 structure; the identity of direct DDR2 kinase substrates beyond autophosphorylation; and whether kinase-independent and kinase-dependent DDR2 functions can be therapeutically dissected.
  • No full-length DDR2 structure exists
  • Direct kinase substrates remain largely unidentified
  • Transmembrane activation mechanism unresolved
  • Therapeutic window between kinase-dependent and kinase-independent functions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0060089 molecular transducer activity 5 GO:0098631 cell adhesion mediator activity 4
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 3 GO:0031012 extracellular matrix 3 GO:0005576 extracellular region 1
Pathway
R-HSA-162582 Signal Transduction 12 R-HSA-1474244 Extracellular matrix organization 5 R-HSA-1643685 Disease 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1500931 Cell-Cell communication 2 R-HSA-168256 Immune System 2
Partners
CTNNB1DDR1NRP1PLXNA1SHC1SHP2SNAI1SRC
Complex memberships
DDR2-Nrp1-PlexinA1

Evidence

Reading pass · 54 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 DDR1 and DDR2 are receptor tyrosine kinases activated by native triple-helical collagen (not soluble growth factors); collagen activation of DDR2 upregulates matrix metalloproteinase-1 (MMP-1) expression, establishing DDR2 as a collagen receptor that controls cellular responses to the ECM. Receptor-ligand binding assays, kinase activation assays, MMP-1 reporter assays in cell lines Molecular cell High 9659899
2002 DDR2 requires Src kinase activity to be maximally tyrosine-phosphorylated following collagen activation; activated DDR2 associates with the adaptor protein Shc (via a novel Shc domain); Src is required for DDR2-mediated transactivation of the MMP-2 promoter, placing Src and Shc as key signaling intermediates downstream of DDR2. Co-immunoprecipitation, kinase inhibition assays, MMP-2 promoter reporter assays, dominant-negative Src constructs The Journal of biological chemistry High 11884411
2001 DDR2 is induced in hepatic stellate cells upon activation by type I collagen, becomes tyrosine-phosphorylated, and promotes proliferation and Matrigel invasion through increased expression of active MMP-2; a constitutively active chimeric DDR2 recapitulates these effects while kinase-dead DDR2 does not, establishing DDR2 kinase activity as necessary for MMP-2 upregulation and stellate cell activation. Stable overexpression of WT, constitutively active (Fc-DDR2), truncated, and kinase-dead DDR2 constructs; proliferation and invasion assays; MMP-2 activity assays The Journal of clinical investigation High 11696582
2001 DDR2-deficient mice exhibit dwarfism due to reduced chondrocyte proliferation (not aberrant differentiation); DDR2-/- fibroblasts proliferate more slowly than WT, and this defect is rescued by wild-type but not kinase-dead DDR2, demonstrating that DDR2 kinase activity is required for its proliferative function. DDR2 knockout mouse generation, histological analysis, in vitro fibroblast proliferation rescue with WT vs. kinase-dead DDR2 EMBO reports High 11375938
2003 The discoidin domain of DDR2 (but not DDR1) is sufficient for collagen I binding and for transmembrane receptor signaling; three spatially adjacent surface loops within the DDR2 discoidin domain constitute the collagen recognition site, as shown by loop-swap mutagenesis. Recombinant extracellular domain production, solid-phase binding assays, loop-swap mutagenesis, receptor activation assays The Journal of biological chemistry High 12611880
2004 The D2 period of triple-helical collagen II harbors a specific DDR2 binding and autophosphorylation-inducing site; collagen II is a better DDR2 ligand than DDR1; binding is dependent on triple-helical conformation and mediated by the DDR2 discoidin domain. Recombinant collagen II deletion variants, DDR2 binding assays, receptor autophosphorylation assays Journal of molecular biology High 15544808
2006 Collagen X is a ligand for DDR2 (but not DDR1); collagen X binds DDR2 extracellular domain with high affinity and stimulates DDR2 autophosphorylation; unlike fibrillar collagens, the DDR2 discoidin domain alone is not sufficient for collagen X binding, indicating additional DDR2 binding sites; the triple-helical region (but not the NC1 domain) of collagen X activates DDR2. Solid-phase binding assays, DDR2 autophosphorylation assays, domain truncation constructs Matrix biology High 16806867
2008 The minimal collagen sequence GVMGFO (where O = hydroxyproline) is required for DDR2 binding; triple-helical peptides containing this motif both inhibit DDR2 binding to collagen II and activate DDR2 transmembrane signaling, indicating that single triple-helices (not fibrillar collagen) are sufficient for DDR2 activation. Collagen II Toolkit peptide screening, truncated/alanine-substituted peptide binding assays, DDR2 activation assays The Journal of biological chemistry High 18201965
2008 Three missense mutations in the DDR2 kinase domain (T713I, I726R, R752C) causing SMED-SL result in retention of the mutant DDR2 protein in the endoplasmic reticulum and defective collagen-induced receptor activation, identifying ER trafficking failure as a loss-of-function mechanism. Sanger sequencing, expression of mutant DDR2 in human cell lines, subcellular localization, collagen activation assays American journal of human genetics High 19110212
2008 Cell-surface expression of kinase-dead DDR2 (via its extracellular domain) inhibits collagen fibrillogenesis by cells, reducing the rate and abundance of collagen deposition and altering fiber morphology, revealing a kinase-independent structural/regulatory function of the DDR2 extracellular domain in ECM remodeling. Stable mouse osteoblast cell lines expressing kinase-dead DDR2, transmission electron microscopy, fluorescence microscopy, hydroxyproline assays Journal of molecular biology High 18996394
2009 Soluble extracellular domains of DDR1 and DDR2 (naturally shed forms) inhibit collagen fibrillogenesis, reducing collagen deposition and altering fiber morphology and matrix mineralization in osteoblast cell lines. Stable secretion of DDR1/DDR2 ECD, transmission electron microscopy, fluorescence microscopy, hydroxyproline assays Journal of molecular biology High 19900459
2009 Crystal structure of the DDR2 discoidin domain bound to a triple-helical collagen peptide (GVMGFO motif) reveals that two collagen chains are recognized by an amphiphilic pocket delimited by a critical tryptophan residue and a buried salt bridge; collagen binding induces structural changes in DDR2 surface loops potentially linked to receptor activation. X-ray crystallography of DDR2 discoidin domain–collagen peptide complex Structure High 20004161
2009 DDR2 activation by fibrillar collagen I downregulates focal adhesion kinase (FAK) levels in vascular smooth muscle cells; siRNA depletion of DDR2 blocks this FAK downregulation, establishing DDR2 as a regulator of FAK protein levels in collagen-adhered cells. siRNA knockdown of DDR2, Western blotting for FAK, collagen fibril vs. monolayer comparison Biomaterials Medium 19762078
2010 SMED-SL missense mutations: three kinase-domain mutants (T713I, I726R, R752C) are retained in the ER and fail collagen-induced activation; a novel extracellular domain mutant (E113K) traffics normally but fails to bind collagen, demonstrating that SMED-SL arises from at least two distinct loss-of-function mechanisms (ER retention vs. ligand-binding defect). Expression of point mutants in human cell lines, confocal microscopy for localization, collagen binding assays, Western blotting Human molecular genetics High 20223752
2010 ATF4 transcriptionally upregulates DDR2 expression through a C/EBP binding site at -1150 bp in the DDR2 promoter via cooperation with C/EBPβ; DDR2 in turn activates Runx2 through p38 MAPK stimulation to promote osteoblast differentiation. DDR2 promoter deletion/mutation analysis, ATF4/C/EBPβ knockdown and overexpression, p38 MAPK inhibition, osteogenic differentiation assays Journal of bone and mineral research High 20564243
2011 DDR2 activation in preosteoblastic cells promotes osteoblast differentiation by stimulating ERK-mediated phosphorylation of Runx2 (the master osteogenic transcription factor), enhancing its transcriptional activity; constitutively active DDR2 increases bone marker expression while kinase-dead DDR2 blocks DDR2-induced osteogenesis. DDR2 shRNA knockdown, constitutively active DDR2 overexpression, ERK inhibition, Runx2 phosphorylation assays, gain-of-function Runx2 rescue experiments Journal of bone and mineral research High 20734453
2011 DDR2 mutations (e.g., L63V, G505S) found in ~3.8% of squamous cell lung cancers are gain-of-function; expression of mutated DDR2 causes cellular transformation; DDR2-mutant lung cancer cells are selectively killed by RNAi knockdown of DDR2 or by dasatinib treatment, demonstrating oncogenic DDR2 kinase dependency. Sanger sequencing, RNAi knockdown, dasatinib treatment, xenograft tumor models, cellular transformation assays Cancer discovery High 22328973
2011 Collagen I induces DDR1 expression in human lung fibroblasts through a pathway requiring DDR2 activation followed by JAK2 and ERK1/2 signaling; ERK1/2 activation recruits the transcription factor PEBA3 to the DDR1 promoter; DDR2 also mediates collagen I-induced MMP-10 expression through this pathway. DDR2 knockdown, JAK2/ERK inhibitors, DDR1 promoter chromatin immunoprecipitation, gene expression assays The Journal of biological chemistry High 21335558
2012 DDR2 plays a role in fibroblast spreading and migration independent of the adhesion ligand type (fibronectin or collagen) and independent of collagen-induced DDR2 tyrosine kinase activation; DDR2 knockdown also inhibits migration in 3D collagen matrices without affecting matrix contraction. siRNA knockdown of DDR2, 2D migration assays on fibronectin vs. collagen, 3D collagen matrix migration assays Biochemical and biophysical research communications Medium 23131558
2013 DDR2 stabilizes SNAIL1 by stimulating ERK2 activity in a Src-dependent manner; activated ERK2 directly phosphorylates SNAIL1, causing nuclear accumulation, reduced ubiquitylation, and increased protein half-life; this DDR2-ERK2-SNAIL1 axis promotes breast cancer cell invasion, migration, and metastasis in vivo. Co-immunoprecipitation, in vitro ERK2 kinase assays on SNAIL1, cycloheximide chase, ubiquitylation assays, Src inhibition, mouse metastasis models Nature cell biology High 23644467
2013 Quantitative phosphoproteomics of DDR2 signaling identified SHP-2 tyrosine phosphorylation as dependent on DDR2 kinase activity; DDR2 lung cancer mutants L63V and G505S phosphorylate SHP-2, while the I638F kinase-domain mutant shows diminished DDR2 and SHP-2 phosphorylation inversely correlated with clonogenic potential; NCK1, LYN, SHIP-2, and PIK3C2A are also candidate DDR2 signaling nodes. Quantitative mass spectrometry phosphoproteomics (7 time points), biochemical validation of SHP-2 phosphorylation with kinase-dead DDR2, targeted proteomic profiling of DDR2 mutants The Biochemical journal High 23822953
2013 DDR2 mediates collagen-induced upregulation of lysyl oxidase in osteoblasts; collagen advanced glycation (CML-collagen) disrupts DDR2 binding and activation, thereby blocking lysyl oxidase induction, providing a mechanism for reduced enzymatic collagen cross-links in diabetic bone. DDR2 shRNA knockdown in primary osteoblasts, collagen binding assays with glycated vs. non-glycated collagen, lysyl oxidase protein quantification Bone Medium 24120383
2013 Acquired resistance to dasatinib in DDR2-dependent lung cancer cells arises via two mechanisms: (1) a T654I gatekeeper mutation in DDR2, and (2) NF1 loss activating a RAS-ERK bypass pathway, demonstrating that ERK dependency can be achieved downstream of DDR2 through RAS activation. Targeted exome sequencing of resistant cell lines, functional validation of resistance mechanisms, pathway inhibition assays Molecular cancer therapeutics High 24296828
2014 The cytoplasmic juxtamembrane 2 (JM2) region of DDR2 is required for receptor dimerization, which is critical for collagen-induced receptor activation; JM2 is also required for efficient collagen binding to the discoidin domain; expression of JM2-containing peptide inhibits DDR2-mediated MMP-2/9 expression, colony formation, and invasion. JM2 deletion/overexpression constructs, co-immunoprecipitation for dimerization, collagen binding assays, invasion/proliferation assays International journal of cancer Medium 24740739
2014 DDR2 and SRC are direct binding partners; SRC activity is functionally tied to DDR2 activation; dual inhibition of DDR2 and SRC leads to enhanced suppression of DDR2-mutant lung cancer cell lines compared to DDR2 inhibition alone. Co-immunoprecipitation, selective DDR2 inhibitor characterization, dual DDR2/SRC inhibitor assays in cancer cell lines ACS chemical biology Medium 26390252
2014 A novel DDR2 missense mutation (c.2468_2469delCT, p.S823Cfs*2) causes ER retention of the mutant protein, defective N-glycosylation processing, and loss of collagen-induced activation, confirming that DDR2 kinase-domain mutations causing SMED-SL converge on ER trafficking defects. Sanger sequencing, confocal microscopy for subcellular localization, deglycosylation assay, Western blotting, collagen activation assay BMC medical genetics Medium 24725993
2015 DDR2 facilitates HCC invasion, migration, and EMT via activation of ERK2 and stabilization of SNAIL1 protein; DDR2 upregulates MT1-MMP and MMP2 expression through ERK2/SNAIL1 signaling; collagen I can induce the DDR2/ERK2/SNAIL1 signaling cascade in HCC cells. DDR2 overexpression/knockdown, cycloheximide chase for SNAIL1 stability, ERK2 inhibition, Western blotting, invasion/migration assays Journal of experimental & clinical cancer research Medium 26362312
2015 DDR2 suppresses osteoclastogenesis by forming a DDR2-Nrp1-PlexinA1 complex; DDR2 facilitates binding of Nrp1 to PlexinA1, blocking PlexinA1-mediated osteoclast stimulation; DDR2 also prevents PlexinA1 from interacting with TREM2 and DAP12; adenoviral DDR2 delivery to bone alleviates osteopenic phenotypes in ovariectomized mice. Co-immunoprecipitation for complex formation, DDR2 overexpression/RNAi, Nrp1 knockdown rescue assays, in vivo adenoviral delivery, osteoclast differentiation assays Science signaling High 25805889
2015 DDR2 can synergize TGF-β and fibrillar collagen signals to stimulate lung fibroblast myofibroblastic differentiation and VEGF expression; DDR2 knockdown by siRNA or kinase inhibition reduces established lung fibrosis in vivo. In vitro fibroblast stimulation assays, DDR2 siRNA in vivo delivery, bleomycin lung fibrosis mouse model Molecular therapy Medium 27350126
2015 DDR2 inhibition in murine melanoma cells suppresses collagen I-induced migration and invasion by reducing MMP2/9 expression through the ERK1/2 and NF-κB signaling pathways; DDR2 is phosphorylated by collagen I in these cells. DDR2 siRNA knockdown, migration/invasion assays, ERK1/2 and NF-κB pathway inhibition, MMP2/9 expression analysis Acta biochimica et biophysica Sinica Medium 25733533
2015 Neuropilin-1 (Nrp1) co-localizes with DDR2 at the cell membrane, enhances DDR2 phosphorylation and ERK1/2-Runx2 signaling, and prolongs DDR2 protein half-life (post-translational stabilization) without altering DDR2 mRNA levels, thereby promoting osteoblast differentiation. Nrp1 overexpression/silencing, DDR2 half-life assay (cycloheximide chase), immunofluorescence co-localization, ERK1/2 and Runx2 phosphorylation analysis Cellular physiology and biochemistry Medium 25924845
2016 In C. elegans, DDR-2 (the DDR2 ortholog) functions upstream of the Met-like RTK SVH-2 and the scaffold protein SHC-1 in regulating axon regeneration; SHC-1 interacts with both DDR-2 and SVH-2; overexpression of svh-2 and shc-1 suppresses the axon regeneration delay in ddr-2 mutants, placing DDR-2 upstream of the SVH-2-JNK MAPK pathway. C. elegans genetics (ddr-2 mutants, epistasis), axon regeneration assays, co-immunoprecipitation of DDR-2 and SHC-1/SVH-2 PLoS genetics High 27984580
2016 DDR2 in cancer-associated fibroblasts (CAFs) is critical for extracellular matrix production and collagen fiber organization; in tumor cells, DDR2 in basal epithelial cells regulates collective invasion of tumor organoids; both tumor-cell-intrinsic and stromal DDR2 functions are required for breast cancer metastasis in vivo. Genetic cell-type-specific DDR2 deletion, tumor organoid invasion assays, second-harmonic generation microscopy for collagen fiber analysis, mouse metastasis models Cell reports High 27264173
2016 In rheumatoid arthritis fibroblast-like synoviocytes, collagen II-activated phospho-DDR2 induces CYR61 expression via AP-1 transcription factor; elevated CYR61 then accelerates MMP1 production via ETS1; CYR61 shRNA in vivo reduces arthritis severity and bone erosion. DDR2 activation/inhibition, AP-1 and ETS1 reporter assays, CYR61 shRNA adenovirus in CIA rat model, μCT bone analysis Journal of bone and mineral research High 27653023
2017 DDR2 maintains a fibroblastic phenotype with collagen deposition in breast cancer-associated mesenchymal stem cells (MSCs); loss of DDR2 in MSCs impairs their ability to promote DDR2 phosphorylation in breast cancer cells, BC cell alignment, migration, and metastasis; ddr2-deficient (slie) mice show inefficient spontaneous BC metastasis. DDR2 knockdown in MSCs, co-culture assays with BC cells, slie mouse spontaneous metastasis model, phospho-DDR2 Western blotting Cell reports High 28147276
2017 DDR2 facilitates papillary thyroid carcinoma EMT by activating ERK2 and stabilizing Snail1 protein; ERK2 or Snail1 inhibition abrogates DDR2-induced EMT; DDR2 overexpression decreases E-cadherin and increases vimentin expression. Lentiviral DDR2 overexpression, ERK2/Snail1 inhibition, Western blotting, migration/invasion assays Oncology letters Medium 29250189
2018 DDR1 and DDR2 physically interact (co-immunoprecipitation); co-expression of DDR1 and DDR2 produces higher ERK activation than either alone after collagen I stimulation, but inhibits cell proliferation; DDR1 (not DDR2) mediates cell adhesion to collagen I matrix. Co-immunoprecipitation, HEK293T co-overexpression, ERK/JAK2 activation assays, proliferation and adhesion assays with dominant-negative constructs Cell adhesion & migration Medium 29616590
2018 DDR2 gain-of-function variants (L610P or Y740C) causing Warburg-Cinotti syndrome lead to increased DDR2 phosphorylation in patient fibroblasts, indicating reduced receptor autoinhibition and ligand-independent kinase activation; dasatinib prevents DDR2 autophosphorylation in these cells. Phosphorylation analysis in patient-derived fibroblasts, dasatinib treatment, analysis of signaling pathway activation American journal of human genetics High 30449416
2018 Coupling of the GVMGFO-containing triple-helical peptide to crosslinked collagen films restores DDR2 binding and activates DDR2 (phosphorylation of Y740) in COS-7 and HEK293 cells, identifying Y740 as a key DDR2 autophosphorylation site relevant to receptor activation. Photoreactive peptide coupling, DDR2 binding assays, Western blotting for pY740, cell-based DDR2 activation assays Biomaterials Medium 30099278
2018 WRG-28, a small molecule targeting the DDR2 extracellular domain, allosterically inhibits DDR2-collagen receptor-ligand interactions and blocks tumor invasion, migration, and metastatic lung colonization, demonstrating that allosteric extracellular inhibition of DDR2 is functionally effective. Small molecule screening, DDR2 binding assays, tumor invasion/migration assays, in vivo lung colonization assays Proceedings of the National Academy of Sciences High 30061414
2019 DDR2 in CAFs controls breast tumor stiffness by reorganizing collagen fibers at the tumor-stromal boundary through regulation of integrin activation; DDR2 influences mechanotransduction by controlling Rap1-mediated Talin1 and Kindlin2 recruitment to activate collagen-binding integrins. DDR2 depletion in mouse/human CAFs, second-harmonic generation microscopy for collagen fiber analysis, atomic force microscopy for stiffness, Rap1/Talin1/Kindlin2 activation assays, in vivo tumor models eLife High 31144616
2019 DDR2 depletion in tumors increases CD8+ T cell infiltration and sensitizes tumors to anti-PD-1 immunotherapy across five tumor histologies; dasatinib (DDR2 inhibitor) combined with anti-PD-1 reduces tumor load, identifying DDR2 as a regulator of the immunosuppressive tumor microenvironment. In vivo shRNA screen, isogenic mouse tumor models, CyTOF immune cell profiling, RNA-seq, dasatinib + anti-PD-1 combination treatment Science advances High 30801016
2020 DDR2 in cardiac fibroblasts acts via ERK1/2 MAPK-activated SRF transcription factor to enhance expression of anti-apoptotic cIAP2 (conferring resistance to oxidative injury) and to upregulate Skp2, which degrades the CDK inhibitor p27 to promote G1-S cell cycle transition; collagen type I binding to DDR2 is required for these effects. DDR2 knockdown/overexpression, SRF promoter binding assays, ERK1/2 inhibition, WRG-28 DDR2 inhibitor, flow cytometry, Rb phosphorylation assays American journal of physiology. Heart and circulatory physiology Medium 32412792
2021 DDR-mediated matrix resistance (MMDR) to BRAF inhibition in melanoma is mediated by drug-induced linear clustering of phosphorylated DDR1 and DDR2; DDR-dependent MMDR activates a pro-survival NIK/IKKα/NF-κB2 pathway; depletion or pharmacological targeting of DDR overcomes ECM-mediated resistance. DDR1/DDR2 depletion, phospho-DDR imaging, NIK/IKKα/NF-κB2 pathway analysis, xenograft models with imatinib + BRAF inhibitor combination EMBO molecular medicine High 34957688
2021 Tyrosine kinase-independent functions of DDR2 in tumor cells support Matrigel invasion and in vivo metastasis; paracrine DDR2 signaling between tumor cells and CAFs also supports invasion and lung colonization; these findings suggest kinase-independent DDR2 activities contribute to metastasis. Kinase-dead DDR2 rescue in tumor cells, conditioned media experiments, in vivo lung colonization assays Journal of cell science Medium 34477203
2021 EMT regulators TWIST and SNAIL induce DDR2 expression; DDR2 upregulation in recurrent breast tumor cells activates YAP/TAZ signaling; DDR2 knockdown reduces both clonogenic growth and ferroptosis sensitivity; erastin-induced DDR2 upregulation and phosphorylation occur independently of collagen I. DDR2 knockdown, TWIST/SNAIL overexpression, YAP/TAZ inhibition, ferroptosis (erastin) assays, clonogenic growth assays Oncogene Medium 33603168
2022 DDR2 in ovarian cancer CAFs promotes collagen production through arginase activity; DDR2-depleted CAFs show decreased ornithine and polyamine levels leading to reduced collagen production; SNAI1 protein is detected at the arginase-1 promoter and DDR2-depleted CAFs have decreased SNAI1 at this promoter, revealing DDR2 regulates arginase-1 transcription via SNAI1. DDR2 depletion in human/mouse CAFs, arginase activity assays, metabolomics (ornithine/polyamine), ChIP for SNAI1 at arginase-1 promoter, conditioned media tumor invasion assays Oncogene High 37996700
2022 DDR2 in ovarian cancer CAFs promotes tumor cell invasion through regulation of periostin (POSTN) expression via integrin β1 (ITGB1); DDR2-expressing fibroblasts enhance mesothelial cell clearance and tumor cell invasion three-fold; DDR2 regulation of POSTN is mediated through ITGB1. DDR2 and POSTN knockdown in CAFs, co-culture mesothelial clearance assays, in vivo co-injection xenograft models, ITGB1 pathway analysis Cancers Medium 35884543
2022 CEBPA-DT lncRNA promotes DDR2 expression by binding hnRNPC, facilitating cytoplasmic translocation of hnRNPC which enhances hnRNPC-DDR2 mRNA interaction; DDR2 then promotes β-catenin nuclear translocation through a DDR2-β-catenin protein interaction, activating Snail1 transcription to drive EMT and HCC metastasis. RNA pull-down, RIP, co-immunoprecipitation for DDR2-β-catenin interaction, immunofluorescence for β-catenin localization, DDR2 inhibitor treatment, subcellular fractionation Journal of experimental & clinical cancer research Medium 36471363
2022 Nilotinib inhibits DDR2 in human valvular interstitial cells (VICs); DDR2 inhibition or selective DDR2 targeting in VICs induces osteogenic activation and calcification; increasing DDR2 ligand (collagen) blunts this osteogenic response, establishing DDR2 as a suppressor of VIC calcification. DDR2 selective inhibition in human VICs, osteogenic/calcification assays, transcriptomic target identification, collagen rescue experiments British journal of pharmacology Medium 35751904
2023 DDR2 in ovarian cancer omental fibroblasts regulates glycolysis through an AKT/SNAI1 axis, suppressing fructose-1,6-bisphosphatase and increasing hexokinase activity; DDR2 inhibition decreases protein synthesis and secretion, including LOXL2; adding back LOXL2 to DDR2-deficient fibroblasts rescues tumor cell invasion. DDR2 depletion, glycolytic enzyme activity assays, secretome proteomics, LOXL2 rescue experiments, in vivo peritoneal metastasis model Molecular cancer research Medium 37527178
2023 DDR2 in gastric cancer promotes stemness by mediating SOX2 expression; DDR2 governs EMT programming through recruiting an NFATc1-SOX2 complex to the Snai1 promoter; DDR2-mTOR-SOX2 axis controls cancer stem cell autophagy and DNA damage responses; miR-199a-3p directly targets DDR2. Luciferase reporter assays for miR-199a-3p/DDR2 targeting, DDR2 knockdown/overexpression, NFATc1-SOX2 complex ChIP at Snai1 promoter, orthotopic xenograft peritoneal dissemination model Cellular signalling Medium 36813149
2024 DDR2 induces STAT3 phosphorylation and nuclear translocation; activated STAT3 enhances DDR2 expression, forming a positive feedback loop in oxaliplatin-resistant HCC; STAT3 directly enhances transcription of PD-L1 and CCL20 (recruiting PMN-MDSCs) via dual luciferase reporter assays, establishing a DDR2/STAT3/PD-L1/CCL20 immunosuppressive axis. DDR2/STAT3 knockdown, phospho-STAT3 analysis, luciferase reporter assays for PD-L1 and CCL20 promoters, MDSC transwell migration assays, in vivo tumor models Cellular and molecular gastroenterology and hepatology Medium 38969205
2004 DDR1 and DDR2 overexpression in human smooth muscle cells reduces collagen expression and induces MMP-1 at mRNA and protein levels; DDR2 (but not DDR1) specifically enhances MMP-2 activation and increases collagen and elastin degradation, demonstrating paralog-specific ECM remodeling functions. Retroviral overexpression of DDR1 and DDR2 in human SMCs on polymerized collagen gels, MMP-1/MMP-2 RT-PCR and protein assays, collagen/elastin degradation assays The American journal of pathology Medium 15111304

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1997 The discoidin domain receptor tyrosine kinases are activated by collagen. Molecular cell 803 9659899
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2011 Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer discovery 379 22328973
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
1996 Generation and analysis of 280,000 human expressed sequence tags. Genome research 376 8889549
2014 A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways. Cell 325 25036637
2013 The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis. Nature cell biology 321 23644467
2006 Sensing extracellular matrix: an update on discoidin domain receptor function. Cellular signalling 273 16626936
2013 New targetable oncogenes in non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 259 23401445
2001 DDR2 receptor promotes MMP-2-mediated proliferation and invasion by hepatic stellate cells. The Journal of clinical investigation 213 11696582
2001 The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism. EMBO reports 209 11375938
2017 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation. Molecular cell 185 28890335
2003 Molecular analysis of collagen binding by the human discoidin domain receptors, DDR1 and DDR2. Identification of collagen binding sites in DDR2. The Journal of biological chemistry 165 12611880
2008 Characterization of high affinity binding motifs for the discoidin domain receptor DDR2 in collagen. The Journal of biological chemistry 155 18201965
2013 Discoidin domain receptors in disease. Matrix biology : journal of the International Society for Matrix Biology 153 24361528
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2004 Role of discoidin domain receptors 1 and 2 in human smooth muscle cell-mediated collagen remodeling: potential implications in atherosclerosis and lymphangioleiomyomatosis. The American journal of pathology 135 15111304
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2007 Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma. British journal of cancer 114 17299390
2019 Targeting DDR2 enhances tumor response to anti-PD-1 immunotherapy. Science advances 108 30801016
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2009 Crystallographic insight into collagen recognition by discoidin domain receptor 2. Structure (London, England : 1993) 108 20004161
2006 The discoidin domain receptor DDR2 is a receptor for type X collagen. Matrix biology : journal of the International Society for Matrix Biology 105 16806867
2002 Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen. The Journal of biological chemistry 105 11884411
2017 Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth. Cell reports 96 28147276
2019 DDR2 controls breast tumor stiffness and metastasis by regulating integrin mediated mechanotransduction in CAFs. eLife 94 31144616
2018 TIM-1 Ubiquitination Mediates Dengue Virus Entry. Cell reports 94 29742433
2011 An essential role of discoidin domain receptor 2 (DDR2) in osteoblast differentiation and chondrocyte maturation via modulation of Runx2 activation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 91 20734453
2021 DDR2 upregulation confers ferroptosis susceptibility of recurrent breast tumors through the Hippo pathway. Oncogene 89 33603168
2016 The Action of Discoidin Domain Receptor 2 in Basal Tumor Cells and Stromal Cancer-Associated Fibroblasts Is Critical for Breast Cancer Metastasis. Cell reports 89 27264173
2018 Inhibition of tumor-microenvironment interaction and tumor invasion by small-molecule allosteric inhibitor of DDR2 extracellular domain. Proceedings of the National Academy of Sciences of the United States of America 87 30061414
2017 The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery. Nature communications 86 29180619
2008 Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications. American journal of human genetics 86 19110212
2019 Transketolase (TKT) activity and nuclear localization promote hepatocellular carcinoma in a metabolic and a non-metabolic manner. Journal of experimental & clinical cancer research : CR 78 30971297
2004 The D2 period of collagen II contains a specific binding site for the human discoidin domain receptor, DDR2. Journal of molecular biology 72 15544808
2021 The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer. International journal of molecular sciences 70 34207360
1993 Structure, expression and chromosomal mapping of TKT from man and mouse: a new subclass of receptor tyrosine kinases with a factor VIII-like domain. Oncogene 70 8247548
2015 DDR2 facilitates hepatocellular carcinoma invasion and metastasis via activating ERK signaling and stabilizing SNAIL1. Journal of experimental & clinical cancer research : CR 69 26362312
2010 Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK-mediated Runx2 activation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 68 20564243
2008 A novel dwarfism with gonadal dysfunction due to loss-of-function allele of the collagen receptor gene, Ddr2, in the mouse. Molecular endocrinology (Baltimore, Md.) 67 18483174
2010 Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients. Human molecular genetics 66 20223752
2013 Phosphoproteomics of collagen receptor networks reveals SHP-2 phosphorylation downstream of wild-type DDR2 and its lung cancer mutants. The Biochemical journal 64 23822953
2014 Discoidin domain receptor 2 (DDR2) promotes breast cancer cell metastasis and the mechanism implicates epithelial-mesenchymal transition programme under hypoxia. The Journal of pathology 63 25130389
2015 Tyrosine kinase discoidin domain receptors DDR1 and DDR2 are coordinately deregulated in triple-negative breast cancer. Breast cancer research and treatment 62 25667101
2016 Targeting of Discoidin Domain Receptor 2 (DDR2) Prevents Myofibroblast Activation and Neovessel Formation During Pulmonary Fibrosis. Molecular therapy : the journal of the American Society of Gene Therapy 59 27350126
2011 Collagen I induces discoidin domain receptor (DDR) 1 expression through DDR2 and a JAK2-ERK1/2-mediated mechanism in primary human lung fibroblasts. The Journal of biological chemistry 58 21335558
2016 Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination. Scientific reports 57 26934957
2015 DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-κB pathway. Acta biochimica et biophysica Sinica 54 25733533
2009 Inhibition of collagen fibrillogenesis by cells expressing soluble extracellular domains of DDR1 and DDR2. Journal of molecular biology 52 19900459
2015 Characterization of DDR2 Inhibitors for the Treatment of DDR2 Mutated Nonsmall Cell Lung Cancer. ACS chemical biology 49 26390252
2021 Targeting Discoidin Domain Receptors DDR1 and DDR2 overcomes matrix-mediated tumor cell adaptation and tolerance to BRAF-targeted therapy in melanoma. EMBO molecular medicine 48 34957688
2022 LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/β-catenin activation via interacting with hnRNPC. Journal of experimental & clinical cancer research : CR 45 36471363
2013 Acquired resistance to dasatinib in lung cancer cell lines conferred by DDR2 gatekeeper mutation and NF1 loss. Molecular cancer therapeutics 45 24296828
2011 Osteoarthritis-like changes in the heterozygous sedc mouse associated with the HtrA1-Ddr2-Mmp-13 degradative pathway: a new model of osteoarthritis. Osteoarthritis and cartilage 44 22155431
2013 Collagen advanced glycation inhibits its Discoidin Domain Receptor 2 (DDR2)-mediated induction of lysyl oxidase in osteoblasts. Bone 43 24120383
2005 Expression of Discoidin Domain Receptor 2 (DDR2) in the developing heart. Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada 43 16060979
2023 DDR2-regulated arginase activity in ovarian cancer-associated fibroblasts promotes collagen production and tumor progression. Oncogene 42 37996700
2019 Circ-LAMP1 promotes T-cell lymphoblastic lymphoma progression via acting as a ceRNA for miR-615-5p to regulate DDR2 expression. Gene 41 30922709
2014 A host deficiency of discoidin domain receptor 2 (DDR2) inhibits both tumour angiogenesis and metastasis. The Journal of pathology 41 24293323
2016 Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects. American journal of human genetics 39 27259054
2014 Adaptive responses to dasatinib-treated lung squamous cell cancer cells harboring DDR2 mutations. Cancer research 36 25348954
2018 Distribution of KRAS, DDR2, and TP53 gene mutations in lung cancer: An analysis of Iranian patients. PloS one 35 30048458
2009 The relative roles of collagen adhesive receptor DDR2 activation and matrix stiffness on the downregulation of focal adhesion kinase in vascular smooth muscle cells. Biomaterials 34 19762078
2014 Overexpression of DDR2 contributes to cell invasion and migration in head and neck squamous cell carcinoma. Cancer biology & therapy 33 24556606
2014 Identification of type II and III DDR2 inhibitors. Journal of medicinal chemistry 32 24754677
2014 Identification of novel driver mutations of the discoidin domain receptor 2 (DDR2) gene in squamous cell lung cancer of Chinese patients. BMC cancer 32 24885564
2008 Regulation of collagen fibrillogenesis by cell-surface expression of kinase dead DDR2. Journal of molecular biology 32 18996394
2016 DDR2 Induces Gastric Cancer Cell Activities via Activating mTORC2 Signaling and Is Associated with Clinicopathological Characteristics of Gastric Cancer. Digestive diseases and sciences 31 27010547
2015 Molecular genetic studies on EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 in primary pulmonary adenoid cystic carcinoma. Diagnostic pathology 31 26373952
2021 TKT maintains intestinal ATP production and inhibits apoptosis-induced colitis. Cell death & disease 30 34535624
2015 DDR2 (discoidin domain receptor 2) suppresses osteoclastogenesis and is a potential therapeutic target in osteoporosis. Science signaling 30 25805889
2022 DDR2 Expression in Cancer-Associated Fibroblasts Promotes Ovarian Cancer Tumor Invasion and Metastasis through Periostin-ITGB1. Cancers 27 35884543
2018 Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-Cell Targets in Human IDH-Mutant Glioma. Clinical cancer research : an official journal of the American Association for Cancer Research 26 29563135
2016 Targeting DDR2 in head and neck squamous cell carcinoma with dasatinib. International journal of cancer 26 27434411
2014 A novel mutation in DDR2 causing spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications (SMED-SL) results in defective intra-cellular trafficking. BMC medical genetics 26 24725993
2000 Upregulation of tyrosine kinase TKT by the Epstein-Barr virus transactivator Zta. Journal of virology 26 10906192
2018 DDR1 and DDR2 physical interaction leads to signaling interconnection but with possible distinct functions. Cell adhesion & migration 25 29616590
2016 DDR2-CYR61-MMP1 Signaling Pathway Promotes Bone Erosion in Rheumatoid Arthritis Through Regulating Migration and Invasion of Fibroblast-Like Synoviocytes. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 25 27653023
2024 TKT-PARP1 axis induces radioresistance by promoting DNA double-strand break repair in hepatocellular carcinoma. Oncogene 24 38216672
2015 NSCLC Driven by DDR2 Mutation Is Sensitive to Dasatinib and JQ1 Combination Therapy. Molecular cancer therapeutics 24 26206333
2014 The intracellular juxtamembrane domain of discoidin domain receptor 2 (DDR2) is essential for receptor activation and DDR2-mediated cancer progression. International journal of cancer 24 24740739
2010 The collagen receptor DDR2 is expressed during early cardiac development. Anatomical record (Hoboken, N.J. : 2007) 23 19479965
1996 Structure and functional analysis of the multistress response gene DDR2 from Saccharomyces cerevisiae. Biochemical and biophysical research communications 23 8954934
2019 Parity predisposes breasts to the oncogenic action of PAPP-A and activation of the collagen receptor DDR2. Breast cancer research : BCR 22 31046834
2016 Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors. Chemical biology & drug design 22 27589335
1993 Nucleotide sequence of the Escherichia coli K-12 transketolase (tkt) gene. Biochimica et biophysica acta 22 8241274
1993 Two open reading frames adjacent to the Escherichia coli K-12 transketolase (tkt) gene show high similarity to the mannitol phosphotransferase system enzymes from Escherichia coli and various gram-positive bacteria. Biochimica et biophysica acta 22 8353127
2016 The C. elegans Discoidin Domain Receptor DDR-2 Modulates the Met-like RTK-JNK Signaling Pathway in Axon Regeneration. PLoS genetics 21 27984580
2010 Expression of discoidin domain receptors (DDR2) in alcoholic liver fibrosis in rats. Archives of medical research 21 21199726
2023 Stromal DDR2 Promotes Ovarian Cancer Metastasis through Regulation of Metabolism and Secretion of Extracellular Matrix Proteins. Molecular cancer research : MCR 19 37527178
2022 Nuclear Tkt promotes ischemic heart failure via the cleaved Parp1/Aif axis. Basic research in cardiology 19 35380314
2020 Discoidin Domain Receptors, DDR1b and DDR2, Promote Tumour Growth within Collagen but DDR1b Suppresses Experimental Lung Metastasis in HT1080 Xenografts. Scientific reports 19 32047176
2012 Discoidin domain receptor 2 (DDR2) regulates proliferation of endochondral cells in mice. Biochemical and biophysical research communications 19 23022180
1998 The mouse transketolase (TKT) gene: cloning, characterization, and functional promoter analysis. Genomics 19 9521875
2023 Exploring the Cellular and Molecular Mechanism of Discoidin Domain Receptors (DDR1 and DDR2) in Bone Formation, Regeneration, and Its Associated Disease Conditions. International journal of molecular sciences 18 37834343
2018 DDR1 and DDR2 in skin. Cell adhesion & migration 18 29952722
2018 Recurrent, Activating Variants in the Receptor Tyrosine Kinase DDR2 Cause Warburg-Cinotti Syndrome. American journal of human genetics 18 30449416
2017 DDR2 facilitates papillary thyroid carcinoma epithelial mesenchymal transition by activating ERK2/Snail1 pathway. Oncology letters 18 29250189
2024 DDR2/STAT3 Positive Feedback Loop Mediates the Immunosuppressive Microenvironment by Upregulating PD-L1 and Recruiting MDSCs in Oxaliplatin-Resistant HCC. Cellular and molecular gastroenterology and hepatology 17 38969205
2021 Tyrosine kinase-independent actions of DDR2 in tumor cells and cancer-associated fibroblasts influence tumor invasion, migration and metastasis. Journal of cell science 17 34477203
2020 Coordinated regulation of cell survival and cell cycle pathways by DDR2-dependent SRF transcription factor in cardiac fibroblasts. American journal of physiology. Heart and circulatory physiology 17 32412792
2022 COL10A1-DDR2 axis promotes the progression of pancreatic cancer by regulating MEK/ERK signal transduction. Frontiers in oncology 16 36530986
2016 Functional Analyses of Mutations in Receptor Tyrosine Kinase Genes in Non-Small Cell Lung Cancer: Double-Edged Sword of DDR2. Clinical cancer research : an official journal of the American Association for Cancer Research 16 26826182
2015 Nrp1, a Neuronal Regulator, Enhances DDR2-ERK-Runx2 Cascade in Osteoblast Differentiation via Suppression of DDR2 Degradation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 16 25924845
2014 Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements. PloS one 16 24505276
2012 DDR2 plays a role in fibroblast migration independent of adhesion ligand and collagen activated DDR2 tyrosine kinase. Biochemical and biophysical research communications 16 23131558
2005 RpoS-mediated growth-dependent expression of the Escherichia coli tkt genes encoding transketolases isoenzymes. Current microbiology 16 15968503
2013 Discoidin domain receptor 2 (DDR2) regulates body size and fat metabolism in mice. Transgenic research 15 24036888
2010 Discoidin domain receptor 2 (DDR2) is required for maintenance of spermatogenesis in male mice. Molecular reproduction and development 15 19681157
2023 FOXA1/MND1/TKT axis regulates gastric cancer progression and oxaliplatin sensitivity via PI3K/AKT signaling pathway. Cancer cell international 14 37817120
2018 Coupling of a specific photoreactive triple-helical peptide to crosslinked collagen films restores binding and activation of DDR2 and VWF. Biomaterials 14 30099278
2024 HMGA1 promotes the progression of esophageal squamous cell carcinoma by elevating TKT-mediated upregulation of pentose phosphate pathway. Cell death & disease 13 39080260
2023 miR-199a-3p promotes gastric cancer progression by promoting its stemness potential via DDR2 mediation. Cellular signalling 13 36813149
2023 Cross species systems biology discovers glial DDR2, STOM, and KANK2 as therapeutic targets in progressive supranuclear palsy. Nature communications 13 37919278
2023 Novel insights into the role of Discoidin domain receptor 2 (DDR2) in cancer progression: a new avenue of therapeutic intervention. Matrix biology : journal of the International Society for Matrix Biology 13 38081526
2021 Amplification of DDR2 mediates sorafenib resistance through NF-κB/c-Rel signaling in hepatocellular carcinoma. Cell biology international 13 33969575
2018 C-MYC, HIF-1α, ERG, TKT, and GSTP1: an Axis in Prostate Cancer? Pathology oncology research : POR 13 30357756
2012 DDR2 polymorphisms and mRNA expression in lung cancers of Japanese patients. Oncology letters 13 22807955
2022 The tyrosine kinase inhibitor nilotinib targets the discoidin domain receptor DDR2 in calcific aortic valve stenosis. British journal of pharmacology 12 35751904
2002 Elevated expression of tyrosine kinase DDR2 in primary biliary cirrhosis. Autoimmunity 12 12765478