Discoidin domain receptor 1 (DDR1) is a collagen activated receptor tyrosine kinase (RTK) which controls cellular proliferation and migration. DDR1 plays important roles in organogenesis and wound healing. Furthermore, aberrant DDR1 signalling is implicated in the progression and poor prognosis of several diseases, including organ fibroses and cancers. DDR1 is therefore an attractive target for pharmacological intervention. However, unlike in many other RTKs, the regulatory mechanisms underpinning DDR1 signalling are poorly understood. This project investigated the regulatory function of the long intracellular juxtamembrane (JM) region of DDR1. The kinase proximal JM segment, termed JM4, is shown to be an important regulator of DDR1 kinase activity. A 2.58 Å resolution crystal structure revealed that the JM4 segment forms a hairpin which enters the kinase active site and reinforces activation loop autoinhibition. Enzymological analysis of purified DDR1 constructs demonstrated that this autoinhibition is relieved in an ordered process which begins with the rapid, in cis, phosphorylation of the JM4 segment (Tyr569 and Tyr586), followed by slow, in trans, phosphorylation of the activation loop (Tyr796). Both successive phosphorylation events are shown to have drastic activating effects on the kinase catalytic rate. Analysis of cell expressed DDR1 also revealed that JM4 Tyr mutation (DDR1-Y569F/Y586F) abolishes collagen induced receptor activation. A secondary positive role for the JM4 region in DDR1 activation is also identified through cell-based analysis. This role could be the recruitment of Src, a non-receptor tyrosine kinase, which is shown to be an activator of DDR1, but not DDR1-Y569F/Y586F, signalling. The identification of the DDR1 JM4 region as a regulator of receptor signalling provides an interesting avenue for the development of DDR1-specific kinase inhibitors.