DDR1 and DDR2 are RTKs comprising an extracellular Discoidin (DS) homology domain that encompasses the collagen-binding site, a DS-like domain that contributes to collagen-induced receptor activation, an extracellular juxtamembrane region that contains N- and O-glycosylation sites and matrix metalloproteinase cleavage sites. Multiple tyrosine residues within the intracellular juxtamembrane region and tyrosine kinase domain of DDR1 can be phosphorylated and recruit proteins, such as ShcA, SHP-2, and the p85 subunit of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). DDR1 stimulates several signaling pathways in a context- and cell type-dependent manner. For example, DDR1 activates estrogen receptor kinase (ERK) signaling in vascular smooth muscle cells, but inhibits ERK in mesangial cells, and has no effect on ERK activation in T47D breast cancer cells. In addition, DDR1 modulates signaling pathways initiated by other matrix receptors (e.g., integrins), cytokines [e.g., transforming growth factor (TGF)-β], and transmembrane receptors (e.g., Notch1). Interaction of DDR1 with various receptors is important for the regulation of cell survival, migration, and differentiation in development and pathological conditions.


1.Sandeepkumar Kothiwale,et al. Drug Discov Today. 2015 Feb; 20(2): 255–261.