Discoidin domain-containing receptor 1 (DDR1)

Discoidin domain-containing receptor 1 (DDR1) is a unique member of the receptor tyrosine kinase (RTK) family that is activated by various types of collagen rather than soluble growth factors (UniProt Q08345). Unlike most RTKs that exhibit rapid and transient activation, DDR1 displays slow and sustained autophosphorylation upon collagen binding, which triggers signaling cascades involved in cell attachment, migration, and survival (PubMed: 28933000). DDR1 is widely expressed in epithelial cells and plays a pivotal role in regulating cell-extracellular matrix interactions and the expression of matrix metalloproteinases (NCBI Gene ID: 780). In clinical contexts, DDR1 is frequently upregulated in solid tumors, including lung, breast, and pancreatic cancers, where it contributes to the epithelial-to-mesenchymal transition (EMT), chemoresistance, and metastasis (PubMed: 30655531). Beyond oncology, DDR1 is implicated in the progression of fibrotic diseases of the lung, liver, and kidney, as well as inflammatory conditions like atherosclerosis (PubMed: 24551055). Therapeutic strategies primarily focus on small-molecule inhibitors targeting the DDR1 kinase domain to disrupt these pathological signaling pathways (PubChem).

Other names

CD167 antigen-like family member ACell adhesion kinaseEpithelial discoidin domain-containing receptor 1HGK2Mammary carcinoma kinase 10Protein-tyrosine kinase RTK 6Tyrosine kinase DDRTRKEMCK10PTK3

Small molecule inhibition of the intracellular kinase domain to prevent ATP binding and collagen-induced autophosphorylation, thereby disrupting downstream signaling pathways.