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PMID:11375938

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Citation

Labrador, JP, Azcoitia, V, Tuckermann, J, Lin, C, Olaso, E, Mañes, S, Brückner, K, Goergen, JL, Lemke, G, Yancopoulos, G, Angel, P, Martínez, C and Klein, R (2001) The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism. EMBO Rep. 2:446-52

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.

Links

PubMed PMC1083888 Online version:10.1093/embo-reports/kve094

Keywords

Animals; Apoptosis; Bone Development/genetics; Bone Development/physiology; Cell Division; Chondrocytes/metabolism; Chondrocytes/physiology; Collagen/genetics; Collagen/metabolism; Dwarfism/genetics; Dwarfism/physiopathology; Fibroblasts/metabolism; Fibroblasts/physiology; Growth Plate/anatomy & histology; Humerus/growth & development; Immunoblotting; In Situ Hybridization; In Situ Nick-End Labeling; Metatarsal Bones/growth & development; Mice; Mice, Knockout; Receptor Protein-Tyrosine Kinases/genetics; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Mitogen/genetics; Receptors, Mitogen/metabolism; Skin/cytology; Skin/injuries; Skin/metabolism; Tibia/growth & development; Wound Healing

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DDR2

involved_in

GO:0048146: positive regulation of fibroblast proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DDR2

involved_in

GO:0003416: endochondral bone growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DDR2

involved_in

GO:0035988: chondrocyte proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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