Imperial College London

Dr Chris Dunsby

Faculty of Natural SciencesDepartment of Physics

Reader in Biomedical Optics
 
 
 
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Contact

 

+44 (0)20 7594 7755christopher.dunsby Website

 
 
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Location

 

622Blackett LaboratorySouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Corcoran:2019:10.1038/s41598-019-53176-4,
author = {Corcoran, D and Juskaite, V and Xu, Y and Gorlitz, F and Alexandrov, Y and Dunsby, C and French, P and Leitinger, B},
doi = {10.1038/s41598-019-53176-4},
journal = {Scientific Reports},
title = {DDR1 autophosphorylation is a result of aggregation into dense clusters},
url = {http://dx.doi.org/10.1038/s41598-019-53176-4},
volume = {9},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The collagen receptor DDR1 is a receptor tyrosine kinase that promotes progression ofa wide range of human disorders. Little is known about how ligand binding triggers DDR1 kinase activity. We previously reported that collagen induces DDR1 activation through lateral dimer association and phosphorylation between dimers, a process that requires specific transmembrane association. Here we demonstrate ligand-induced DDR1 clustering by widefield and super-resolution imaging and provide evidence for a mechanism whereby DDR1 kinase activity is determined by its molecular density. Ligand binding resulted in initial DDR1 reorganisation into morphologically distinct clusters with unphosphorylated DDR1. Further compaction over time led to clusters with highly aggregated and phosphorylated DDR1. Ligand-induced DDR1 clustering was abolished by transmembrane mutations but did not require kinase activity. Our results significantly advance our understanding of the molecular events underpinning ligand-induced DDR1 kinase activity and provide an explanation for the unusually slow DDR1 activation kinetics.
AU - Corcoran,D
AU - Juskaite,V
AU - Xu,Y
AU - Gorlitz,F
AU - Alexandrov,Y
AU - Dunsby,C
AU - French,P
AU - Leitinger,B
DO - 10.1038/s41598-019-53176-4
PY - 2019///
SN - 2045-2322
TI - DDR1 autophosphorylation is a result of aggregation into dense clusters
T2 - Scientific Reports
UR - http://dx.doi.org/10.1038/s41598-019-53176-4
UR - http://hdl.handle.net/10044/1/74691
VL - 9
ER -