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dc.contributor.authorLuczynski, MT
dc.contributor.authorHarrison, PT
dc.contributor.authorLima, N
dc.contributor.authorKrasny, L
dc.contributor.authorPaul, A
dc.contributor.authorHuang, PH
dc.date.accessioned2018-05-08T09:31:31Z
dc.date.issued2018-06
dc.identifier.citationBiochemical and biophysical research communications, 2018, 501 (1), pp. 124 - 130
dc.identifier.issn0006-291X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1668
dc.identifier.eissn1090-2104
dc.identifier.doi10.1016/j.bbrc.2018.04.191
dc.description.abstractDiscoidin 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.formatPrint-Electronic
dc.format.extent124 - 130
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Membrane
dc.subjectHumans
dc.subjectCollagen
dc.subjectTyrosine
dc.subjectIntegrins
dc.subjectRecombinant Proteins
dc.subjectMicroscopy, Fluorescence
dc.subjectAmino Acid Substitution
dc.subjectMutagenesis, Site-Directed
dc.subjectSignal Transduction
dc.subjectProtein Binding
dc.subjectPhosphorylation
dc.subjectMutant Proteins
dc.subjectHEK293 Cells
dc.subjectSrc Homology 2 Domain-Containing, Transforming Protein 1
dc.subjectDiscoidin Domain Receptor 2
dc.titleSpatial localisation of Discoidin Domain Receptor 2 (DDR2) signalling is dependent on its collagen binding and kinase activity.
dc.typeJournal Article
dcterms.dateAccepted2018-04-24
rioxxterms.versionofrecord10.1016/j.bbrc.2018.04.191
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBiochemical and biophysical research communications
pubs.issue1
pubs.notesNo 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-statusPublished
pubs.volume501
pubs.embargo.termsNo embargo
icr.researchteamProtein Networksen_US
icr.researchteamMolecular and Systems Oncologyen_US
dc.contributor.icrauthorLuczynski, Maciejen
dc.contributor.icrauthorKrasny, Lukasen
dc.contributor.icrauthorHarrison, Peteren
dc.contributor.icrauthorHuang, Paulen


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