Discoidin domain receptor functions in physiological and pathological conditions

Int Rev Cell Mol Biol. 2014;310:39-87. doi: 10.1016/B978-0-12-800180-6.00002-5.

Abstract

The discoidin domain receptors, DDR1 and DDR2, are nonintegrin collagen receptors that are members of the receptor tyrosine kinase family. Both DDRs bind a number of different collagen types and play important roles in embryo development. Dysregulated DDR function is associated with progression of various human diseases, including fibrosis, arthritis, and cancer. By interacting with key components of the extracellular matrix and displaying distinct activation kinetics, the DDRs form a unique subfamily of receptor tyrosine kinases. DDR-facilitated cellular functions include cell migration, cell survival, proliferation, and differentiation, as well as remodeling of extracellular matrices. This review summarizes the current knowledge of DDR-ligand interactions, DDR-initiated signal pathways and the molecular mechanisms that regulate receptor function. Also discussed are the roles of DDRs in development and disease progression.

Keywords: Cell signaling; Cell–matrix interactions; Receptor activation; Receptor tyrosine kinase; Therapeutic target; Transmembrane collagen receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arthritis / metabolism
  • Atherosclerosis / metabolism
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Collagen / chemistry
  • Discoidin Domain Receptor 1
  • Discoidin Domain Receptors
  • Extracellular Matrix / metabolism
  • Fibrosis / metabolism
  • Gene Expression Regulation*
  • Humans
  • Kidney Diseases / metabolism
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Neoplasms / metabolism
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptors, Mitogen / physiology*
  • Signal Transduction
  • Tissue Distribution

Substances

  • Ligands
  • Receptors, Mitogen
  • Collagen
  • DDR1 protein, human
  • Discoidin Domain Receptor 1
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases