Discoidin domain-containing receptor 1 (DDR1) and Discoidin domain-containing receptor 2 (DDR2) (DDR1/2)

Discoidin domain receptors (DDR1 and DDR2) are a unique subfamily of receptor tyrosine kinases (RTKs) that are activated by various types of collagen rather than soluble growth factors (Vogel et al., 1997, Science). DDR1 is primarily expressed in epithelial cells, while DDR2 is found in mesenchymal cells such as fibroblasts and chondrocytes (Leitinger, 2014, Int Rev Cell Mol Biol). These receptors play critical roles in regulating cell adhesion, migration, proliferation, and extracellular matrix remodeling by acting as sensors for the collagenous environment. In pathological conditions, DDR1 and DDR2 are frequently overexpressed or dysregulated, contributing significantly to cancer progression, epithelial-mesenchymal transition (EMT), and various fibrotic diseases of the lung, liver, and kidney (Valiathan et al., 2012, Cancer Metastasis Rev). Therapeutic targeting of DDRs often involves small molecule kinase inhibitors, many of which were originally developed for other kinases like BCR-ABL or VEGFR, such as dasatinib and nilotinib (Bayer et al., 2019, Cells). However, the development of highly selective DDR inhibitors remains an active area of research to minimize off-target toxicities and specifically modulate collagen-driven disease pathways (Moll et al., 2019, Trends Mol Med).

Other names

MCK10CD167aCell adhesion kinaseEpithelial discoidin domain-containing receptor 1Tyrosine kinase receptor TKTCD167bNeurotrophic tyrosine kinase receptor-related 4Protein-tyrosine kinase RTK 6CAKEDDR1PTK3ATRKETYRO10

ATP-competitive inhibition of the intracellular tyrosine kinase domain, which prevents collagen-induced autophosphorylation and blocks downstream signaling pathways such as MAPK/ERK, PI3K/Akt, and Notch (Leitinger, 2014, Int Rev Cell Mol Biol).