Understanding the structure and function of the DDR1 juxtamembrane region
Lead Research Organisation:
Imperial College London
Department Name: National Heart and Lung Institute
Abstract
Discoidin domain receptors (DDRs) are receptors for the extracellular matrix protein collagen. The DDRs play important roles in development and contribute to disease progression of a number of human diseases. While we have detailed understanding of the interactions between the DDR extracellular region with collagen, not much is known about how collagen binding results in intracellular kinase activation. My lab has discovered that the DDRs are positively regulated by their intracellular juxtamembrane regions. This project will use biochemical and structural approaches to investigate the mechanisms whereby juxtamembrane regions promote DDR activation.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011178/1 | 30/09/2015 | 25/02/2025 | |||
| 1814646 | Studentship | BB/M011178/1 | 30/09/2016 | 31/12/2020 |
| Description | - I have solved an X-ray crystal structure of the intracellular domains of the receptor tyrosine protein I am currently researching - DDR1. - This structure provided insight into the regulation of the kinase by its intracellular juxtamembrane region - Different phosphorylation forms of the kinase have been isolated and analysed for their activity in vitro which has shown that increased phosphorylation increases catalytic rate - The identity of tyrosine residues autophosphroylated in DDR1 have been identified, as has their order of phosphroylation |
| Exploitation Route | The protein I am currently investigation, DDR1, has been implicated in the progression and poor prognosis of numerous diseases which to date have no cure, including cancer and atherosclerosis. An improved understanding of how DDR1 is regulated will provide invaluable insight for the development of pharmacological agents which can target DDR1 in the future. |
| Sectors | Pharmaceuticals and Medical Biotechnology |