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Updated: Feb 11, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
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Spatial localisation of Discoidin Domain Receptor 2 (DDR2) signalling is dependent on its collagen binding and kinase

Maciej T Luczynski1, Peter T Harrison1, Nadia Lima1

  • 1Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom.

Biochemical and Biophysical Research Communications
|May 1, 2018
PubMed

Insights

Discoidin Domain Receptor 2 (DDR2), a collagen-binding kinase, localizes to cell surfaces upon collagen contact. Both collagen binding and kinase activity are essential for DDR2

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Discoidin Domain Receptor 2 (DDR2) is a receptor tyrosine kinase activated by collagen.
  • DDR2 signaling is characterized by delayed and sustained tyrosine phosphorylation.
  • The spatial and temporal regulation of DDR2 activation remains incompletely understood.

Purpose of the Study:

  • To investigate the molecular mechanisms governing the spatiotemporal localization of DDR2 upon collagen stimulation.
  • To elucidate the roles of collagen binding and kinase activity in DDR2 cell surface localization.

Main Methods:

  • Fluorescence microscopy was employed to map the localization of DDR2 and tyrosine phosphorylated proteins.
  • Structure-function analysis was performed using DDR2 mutants with impaired collagen binding or kinase activity.

Main Results:

  • Cellular phosphorylated proteins were found at the interface of DDR2-collagen contact, not in endosomes or lysosomes.
  • DDR2 localization was independent of integrin activation and SHC1.
  • Mutants lacking collagen binding or kinase activity failed to localize to the cell surface.

Conclusions:

  • Both collagen binding and kinase activity are critical for the spatial localization of DDR2.
  • This study reveals key structural features controlling DDR2 activation dynamics.
  • Findings provide novel insights into DDR2 signaling regulation.
Keywords:
CollagenDDR2Discoidin domain receptorReceptor tyrosine kinaseSignal transduction

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