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The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism
Author(s) -
Labrador Juan Pablo,
Azcoitia Valeria,
Tuckermann Jan,
Lin Calvin,
Olaso Elvira,
Mañes Santos,
Brückner Katja,
Goergen JeanLouis,
Lemke Greg,
Yancopoulos George,
Angel Peter,
MartínezA Carlos,
Klein Rüdiger
Publication year - 2001
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kve094
Subject(s) - discoidin domain , biology , microbiology and biotechnology , receptor tyrosine kinase , dwarfism , receptor , extracellular matrix , tyrosine kinase , receptor protein tyrosine kinases , kinase , signal transduction , endocrinology , medicine , genetics , gene
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.