Discoidin domain receptor 1 and Discoidin domain receptor 2 (DDR1 and DDR2)

Discoidin domain receptor 1 and discoidin domain receptor 2 are receptor tyrosine kinases distinguished by an extracellular discoidin (DS) domain that binds collagen. They are atypical among RTKs because they respond to collagen, not growth factors. DDR1 is more commonly expressed in epithelial cells and frequently upregulated in tumor cells, while DDR2 is prevalent in mesenchymal (stromal) cells. Both receptors are implicated in a variety of cellular processes, including cell adhesion, proliferation, migration, differentiation, and regulation of the extracellular matrix. DDR1 has several isoforms, while DDR2 is usually represented by a single functional protein. Dysregulation, overexpression, or mutation of these receptors has been linked to cancer progression, tissue fibrosis, inflammation, and several other diseases, making them validated and emerging targets for therapeutic intervention. Inhibitors that target DDR1 and DDR2 (e.g., imatinib, dasatinib) are being investigated for their potential to treat cancers and fibrotic diseases by disrupting aberrant collagen signaling.

Other names

DDR1: CD167aCluster of differentiation 167aTyrosine-protein kinase TM4SF5Discoidin domain receptor family, member 1DDR2: CD167bTyrosine-protein kinase TYRO10Neurotrophic tyrosine kinase receptor-related 3 (NTRKR3)receptor protein-tyrosine kinase TKTCollagen receptor RTK

Inhibition of DDR1/DDR2 kinase activity, leading to blockade of downstream phosphorylation events and suppression of cell adhesion, migration, and matrix remodeling. Disruption of collagen-induced signaling pathways, impeding processes like metastasis or fibrotic tissue formation