Sensing extracellular matrix: an update on discoidin domain receptor function.
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.
Vogel
Wolfgang F
WF
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario Canada, M5S 1A8. w.vogel@utoronto.ca
Abdulhussein
Rahim
R
Ford
Caroline E
CE
D000818:Animals; D000070818:Discoidin Domain Receptors; D019143:Evolution, Molecular; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D020033:Protein Isoforms; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000378:metabolism*; D015398:Signal Transduction
D020033:Protein Isoforms; D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases