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Spatial localisation of Discoidin Domain Receptor 2 (DDR2) signalling is dependent on its collagen binding and kinase activity.
Luczynski, Maciej T; Harrison, Peter T; Lima, Nadia; Krasny, Lukas; Paul, Angela; Huang, Paul H.
Afiliação
  • Luczynski MT; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom.
  • Harrison PT; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom.
  • Lima N; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom.
  • Krasny L; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom.
  • Paul A; Proteomics Core Facility, The Institute of Cancer Research, London, United Kingdom.
  • Huang PH; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom. Electronic address: paul.huang@icr.ac.uk.
Biochem Biophys Res Commun ; 501(1): 124-130, 2018 06 18.
Article em En | MEDLINE | ID: mdl-29709482
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colágeno / Receptor com Domínio Discoidina 2 Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colágeno / Receptor com Domínio Discoidina 2 Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article