ADAM10 controls collagen signaling and cell migration on collagen by shedding the ectodomain of discoidin domain receptor 1 (DDR1).


Journal Article

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.

Full Text

Cited Authors

  • Shitomi, Y; Thøgersen, IB; Ito, N; Leitinger, B; Enghild, JJ; Itoh, Y

Published Date

  • February 2015

Published In

Volume / Issue

  • 26 / 4

Start / End Page

  • 659 - 673

PubMed ID

  • 25540428

Pubmed Central ID

  • 25540428

Electronic International Standard Serial Number (EISSN)

  • 1939-4586

International Standard Serial Number (ISSN)

  • 1059-1524

Digital Object Identifier (DOI)

  • 10.1091/mbc.e14-10-1463


  • eng