Discoidin domain receptor family member 1 (DDR1) (DDR1)

Discoidin domain receptor family member 1 (DDR1) is a unique receptor tyrosine kinase that is activated by various types of collagen rather than soluble growth factors (UniProt: Q08345). The extracellular domain (ECD) of DDR1 contains a discoidin homology motif that is essential for its interaction with collagen fibers in the extracellular matrix (ECM) (PMID: 28938308). Upon collagen binding to the ECD, DDR1 undergoes a slow and sustained autophosphorylation of its intracellular kinase domain, triggering signaling pathways such as MAPK/ERK and PI3K/Akt that regulate cell adhesion, migration, and survival (PMID: 30107159). DDR1 is predominantly expressed in epithelial cells and plays a vital role in tissue development and wound healing (NCBI Gene: 780). In disease states, DDR1 is often upregulated and contributes significantly to the progression of various cancers, including breast, lung, and pancreatic carcinomas, by promoting metastasis and chemoresistance (PMID: 28938308). It also plays a central role in the pathogenesis of fibrotic diseases, such as idiopathic pulmonary fibrosis and chronic kidney disease, by enhancing collagen production and inflammatory responses (PMID: 30107159). Therapeutic targeting of DDR1 involves small-molecule inhibitors that block its kinase activity or monoclonal antibodies that specifically target the extracellular domain to prevent collagen binding and receptor activation (PMID: 22532586).

Other names

CD167aCAKEDDR1NEPNTRK4PTK3RTK6TRKEDiscoidin domain receptor 1Cell adhesion kinase

Inhibition of collagen-induced receptor autophosphorylation and downstream signaling pathways (PMID: 30107159). Small-molecule inhibitors typically act as ATP-competitive inhibitors of the intracellular kinase domain, while monoclonal antibodies target the extracellular domain to sterically hinder collagen binding and prevent receptor dimerization and activation (PMID: 30107159, PMID: 22532586).