Sensing extracellular matrix: an update on discoidin domain receptor function

Cell Signal. 2006 Aug;18(8):1108-16. doi: 10.1016/j.cellsig.2006.02.012. Epub 2006 Feb 28.


Discoidin Domain Receptors (DDRs) have recently emerged as non-integrin-type receptors for collagen. The two mammalian gene products Discoidin Domain Receptor 1 and -2 constitute a subfamily of tyrosine kinase receptors that are selectively expressed in a number of different cell types and organs. Upon collagen activation, DDRs regulate cell adhesion, proliferation and extracellular matrix remodeling. Here we review the various signaling pathways and cellular responses evoked by activated DDRs. Additionally, we give an overview of the more recent advances in understanding the role of DDRs in various human diseases, in particular during tumor progression, atherosclerosis, inflammation and tissue fibrosis. Furthermore, we discuss potential roles of genes homologous to mammalian DDRs identified in flies, worms and sponges. We show that the structural organization of these DDR-related genes is highly conserved throughout evolution suggesting that invertebrate DDRs may also function as receptors for collagen. By highlighting current questions about these unusual collagen receptors, we hope to attract new research on DDRs from a variety of different fields.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Discoidin Domain Receptors
  • Evolution, Molecular
  • Extracellular Matrix / metabolism*
  • Humans
  • Protein Isoforms
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Mitogen / metabolism*
  • Signal Transduction


  • Protein Isoforms
  • Receptors, Mitogen
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases