RGD Reference Report - Discoidin Domain Receptor 1 Mediates Myosin-Dependent Collagen Contraction. - Rat Genome Database

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Discoidin Domain Receptor 1 Mediates Myosin-Dependent Collagen Contraction.

Authors: Coelho, Nuno M  Arora, Pamma D  van Putten, Sander  Boo, Stellar  Petrovic, Petar  Lin, Alyna Xue  Hinz, Boris  McCulloch, Christopher A 
Citation: Coelho NM, etal., Cell Rep. 2017 Feb 14;18(7):1774-1790. doi: 10.1016/j.celrep.2017.01.061.
RGD ID: 151347403
Pubmed: PMID:28199848   (View Abstract at PubMed)
DOI: DOI:10.1016/j.celrep.2017.01.061   (Journal Full-text)

Discoidin domain receptor 1 (DDR1) is a tyrosine kinase collagen adhesion receptor that mediates cell migration through association with non-muscle myosin IIA (NMIIA). Because DDR1 is implicated in cancer fibrosis, we hypothesized that DDR1 interacts with NMIIA to enable collagen compaction by traction forces. Mechanical splinting of rat dermal wounds increased DDR1 expression and collagen alignment. In periodontal ligament of DDR1 knockout mice, collagen mechanical reorganization was reduced >30%. Similarly, cultured cells with DDR1 knockdown or expressing kinase-deficient DDR1d showed 50% reduction of aligned collagen. Tractional remodeling of collagen was dependent on DDR1 clustering, activation, and interaction of the DDR1 C-terminal kinase domain with NMIIA filaments. Collagen remodeling by traction forces, DDR1 tyrosine phosphorylation, and myosin light chain phosphorylation were increased on stiff versus soft substrates. Thus, DDR1 clustering, activation, and interaction with NMIIA filaments enhance the collagen tractional remodeling that is important for collagen compaction in fibrosis.

Gene-Chemical Interaction Annotations    
lysophosphatidic acid  (EXP,ISO)
nilotinib  (EXP,ISO)

Gene Ontology Annotations    

Biological Process

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Ddr1  (discoidin domain receptor tyrosine kinase 1)

Genes (Mus musculus)
Ddr1  (discoidin domain receptor family, member 1)

Genes (Homo sapiens)
DDR1  (discoidin domain receptor tyrosine kinase 1)

Additional Information