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Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and transmits signals from various collagens in epithelial cells. However, how DDR1-dependent signaling is regulated has not been understood. Here we report that collagen binding induces ADAM10-dependent ectodomain shedding of DDR1. DDR1 shedding is not a result of an activation of its signaling pathway, since DDR1 mutants defective in signaling were shed in an efficient manner. DDR1 and ADAM10 were found to be in a complex on the cell surface, but shedding did not occur unless collagen bound to DDR1. Using a shedding-resistant DDR1 mutant, we found that ADAM10-dependent DDR1 shedding regulates the half-life of collagen-induced phosphorylation of the receptor. Our data also revealed that ADAM10 plays an important role in regulating DDR1-mediated cell adhesion to achieve efficient cell migration on collagen matrices.

Original publication




Journal article


Molecular biology of the cell

Publication Date





659 - 673


Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, United Kingdom.


Humans, Collagen, Receptor Protein-Tyrosine Kinases, Membrane Proteins, Cell Adhesion, Signal Transduction, Cell Movement, Amino Acid Sequence, Protein Structure, Tertiary, Molecular Sequence Data, ADAM Proteins, Amyloid Precursor Protein Secretases, Gene Knockdown Techniques, HEK293 Cells, Discoidin Domain Receptor 1, ADAM10 Protein