| First Author | Olaso E | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 5 | Pages | 3606-13 |
| PubMed ID | 11723120 | Mgi Jnum | J:74327 |
| Mgi Id | MGI:2158097 | Doi | 10.1074/jbc.M107571200 |
| Citation | Olaso E, et al. (2002) Discoidin domain receptor 2 regulates fibroblast proliferation and migration through the extracellular matrix in association with transcriptional activation of matrix metalloproteinase-2. J Biol Chem 277(5):3606-13 |
| abstractText | Discoidin domain receptor 2 (DDR2) is a tyrosine kinase receptor expressed in mesenchymal tissues, the ligand of which is fibrillar collagen. We have compared DDR2 signaling in skin fibroblasts derived from DDR2(-/-) and DDR2(+/-) mice. Proliferation of DDR2(-/-) fibroblasts was significantly decreased compared with DDR2(+/-) cells. DDR2(-/-) fibroblasts exhibited markedly impaired capacity to migrate through a reconstituted basement membrane (Matrigel) in response to a chemotactic stimulus, which correlated with diminished matrix metalloproteinase-2 (MMP-2) activity by gelatin zymography and diminished MMP-2 transcription of a minimal MMP-2 promoter. In contrast, a lack of DDR2 had no effect on cell motility or alpha-smooth muscle actin or vinculin expression. Additionally, expression of type I collagen was greatly reduced in DDR2(-/-) cells. Stable reconstitution of either wild-type DDR2 or constitutively active chimeric DDR2 in DDR2(-/-) cells by retroviral infection restored cell proliferation, migration through a reconstituted basement membrane (Matrigel), and MMP-2 levels to those of DDR2(+/-) fibroblasts. These data establish a role for DDR2 in critical events during wound repair. |
