Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase (RTK) activated by triple-helical collagens that has been implicated in a number of human diseases. Here, high affinity binding of the DDR1 extracellular domains to immobilized type I collagen is reported and the discoid in-collagen affinity quantified in vitro. Residues R105 & S175 and loop regions S52-T57 & R105-K112 in the collagen-binding discoidin domain of DDR1 were shown to be critically involved in collagen binding and receptor activation. Data presented here are the first to report that DDR1 exists as a ligand-independent disulfide-linked dimer. It was found that the stalk region, in particular cysteine residues 303 and 348, are critical to ligand interaction, dimerization and receptor activation. These data suggest DDR1 can form unconventional dimers not predicted by the current ligand-induced RTK dimerization model. This thesis provides new insights into the DDR1 collagen-signaling mechanism which may ultimately lead to the design of therapeutics that interfere with aberrant DDR1 function through disruption of receptor-ligand interaction, dimerization or receptor activation.