title: The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism.
abstract: The discoidin domain receptor 2 (DDR2) is a member of a subfamily of receptor tyrosine kinases whose ligands are fibrillar collagens, and is widely expressed in postnatal tissues. We have generated DDR2-deficient mice to establish the in vivo functions of this receptor, which have remained obscure. These mice exhibit dwarfism and shortening of long bones. This phenotype appears to be caused by reduced chondrocyte proliferation, rather than aberrant differentiation or function. In a skin wound healing model, DDR2-/- mice exhibit a reduced proliferative response compared with wild-type littermates. In vitro, fibroblasts derived from DDR2-/- mutants proliferate more slowly than wild-type fibroblasts, a defect that is rescued by introduction of wild-type but not kinase-dead DDR2 receptor. Together our results suggest that DDR2 acts as an extracellular matrix sensor to modulate cell proliferation.
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Labrador@Socrates.Berkeley.edu
authors.forename: J P
authors.initials: JP
authors.lastname: Labrador
authors.forename: V
authors.initials: V
authors.lastname: Azcoitia
authors.forename: J
authors.initials: J
authors.lastname: Tuckermann
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.forename: E
authors.initials: E
authors.lastname: Olaso
authors.forename: S
authors.initials: S
authors.lastname: Mañes
authors.forename: K
authors.initials: K
authors.lastname: Brückner
authors.forename: J L
authors.initials: JL
authors.lastname: Goergen
authors.forename: G
authors.initials: G
authors.lastname: Lemke
authors.forename: G
authors.initials: G
authors.lastname: Yancopoulos
authors.forename: P
authors.initials: P
authors.lastname: Angel
authors.forename: C
authors.initials: C
authors.lastname: Martínez
authors.forename: R
authors.initials: R
authors.lastname: Klein
mesh_terms: D000818:Animals; D017209:Apoptosis; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D004392:Dwarfism / Q000235:genetics* / Q000503:physiopathology; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D006132:Growth Plate / Q000033:anatomy & histology; D006811:Humerus / Q000254:growth & development; D015151:Immunoblotting; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008682:Metatarsal Bones / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D013977:Tibia / Q000254:growth & development; D014945:Wound Healing
chemical_list: D011975:Receptors, Mitogen; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases