dc.contributor.author | Luczynski, MT | |
dc.contributor.author | Harrison, PT | |
dc.contributor.author | Lima, N | |
dc.contributor.author | Krasny, L | |
dc.contributor.author | Paul, A | |
dc.contributor.author | Huang, PH | |
dc.date.accessioned | 2018-05-08T09:31:31Z | |
dc.date.issued | 2018-06-18 | |
dc.identifier.citation | Biochemical and biophysical research communications, 2018, 501 (1), pp. 124 - 130 | |
dc.identifier.issn | 0006-291X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1668 | |
dc.identifier.eissn | 1090-2104 | |
dc.identifier.doi | 10.1016/j.bbrc.2018.04.191 | |
dc.description.abstract | Discoidin Domain Receptor 2 (DDR2) is a collagen-binding receptor tyrosine kinase that initiates delayed and sustained tyrosine phosphorylation signalling. To understand the molecular basis of this unique phosphorylation profile, here we utilise fluorescence microscopy to map the spatiotemporal localisation of DDR2 and tyrosine phosphorylated proteins upon stimulation with collagen. We show that cellular phosphorylated proteins are localised to the interface where DDR2 is in contact with collagen and not in the early endosomes or lysosomes. We find that DDR2 localisation is independent of integrin activation and the key DDR2 signalling effector SHC1. Structure-function analysis reveals that DDR2 mutants defective for collagen binding or kinase activity are unable to localise to the cell surface, demonstrating for the first time that both collagen binding and kinase functions are required for spatial localisation of DDR2. This study provides new insights into the underlying structural features that control DDR2 activation in space and time. | |
dc.format | Print-Electronic | |
dc.format.extent | 124 - 130 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Membrane | |
dc.subject | Humans | |
dc.subject | Collagen | |
dc.subject | Tyrosine | |
dc.subject | Integrins | |
dc.subject | Recombinant Proteins | |
dc.subject | Microscopy, Fluorescence | |
dc.subject | Amino Acid Substitution | |
dc.subject | Mutagenesis, Site-Directed | |
dc.subject | Signal Transduction | |
dc.subject | Protein Binding | |
dc.subject | Phosphorylation | |
dc.subject | Mutant Proteins | |
dc.subject | HEK293 Cells | |
dc.subject | Src Homology 2 Domain-Containing, Transforming Protein 1 | |
dc.subject | Discoidin Domain Receptor 2 | |
dc.title | Spatial localisation of Discoidin Domain Receptor 2 (DDR2) signalling is dependent on its collagen binding and kinase activity. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-04-24 | |
rioxxterms.versionofrecord | 10.1016/j.bbrc.2018.04.191 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Biochemical and biophysical research communications | |
pubs.issue | 1 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Protein Networks | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular and Systems Oncology | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Protein Networks | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular and Systems Oncology | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.publication-status | Published | |
pubs.volume | 501 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Protein Networks | |
icr.researchteam | Molecular and Systems Oncology | |
dc.contributor.icrauthor | Harrison, Peter | |
dc.contributor.icrauthor | Krasny, Lukas | |
dc.contributor.icrauthor | Huang, Paul | |