| http://purl.uniprot.org/citations/28270508 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28270508 | http://www.w3.org/2000/01/rdf-schema#comment | "Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-bound MMP that is highly expressed in cells with invading capacity, including fibroblasts and invasive cancer cells. However, pathways of MT1-MMP up-regulation are not clearly understood. A potential physiological stimulus for MT1-MMP expression is fibrillar collagen, and it has been shown that it up-regulates both MT1-MMP gene and functions in various cell types. However, the mechanisms of collagen-mediated MT1-MMP activation and its physiological relevance are not known. In this study, we identified discoidin domain receptor 2 (DDR2) as a crucial receptor that mediates this process in human fibroblasts. Knocking down DDR2, but not the β1 integrin subunit, a common subunit for all collagen-binding integrins, inhibited the collagen-induced MT1-MMP-dependent activation of pro-MMP-2 and up-regulation of MT1-MMP at the gene and protein levels. Interestingly, DDR2 knockdown or pharmacological inhibition of DDR2 also inhibited the MT1-MMP-dependent cellular degradation of collagen film, suggesting that cell-surface collagen degradation by MT1-MMP involves DDR2-mediated collagen signaling. This DDR2-mediated mechanism is only present in non-transformed mesenchymal cells as collagen-induced MT1-MMP activation in HT1080 fibrosarcoma cells and MT1-MMP function in MDA-MB231 breast cancer cells were not affected by DDR kinase inhibition. DDR2 activation was found to be noticeably more effective when cells were stimulated by collagen without the non-helical telopeptide region compared with intact collagen fibrils. Furthermore, DDR2-dependent MT1-MMP activation by cartilage was found to be more efficient when the tissue was partially damaged. These data suggest that DDR2 is a microenvironment sensor that regulates fibroblast migration in a collagen-rich environment."xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m116.770057"xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://purl.uniprot.org/core/author | "Ito N."xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://purl.uniprot.org/core/author | "Itoh Y."xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://purl.uniprot.org/core/author | "Gray N.S."xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://purl.uniprot.org/core/author | "Shitomi Y."xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://purl.uniprot.org/core/author | "Majkowska I."xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28270508 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://purl.uniprot.org/core/pages | "6633-6643"xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://purl.uniprot.org/core/title | "Discoidin domain receptor 2 mediates collagen-induced activation of membrane-type 1 matrix metalloproteinase in human fibroblasts."xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://purl.uniprot.org/core/volume | "292"xsd:string |
| http://purl.uniprot.org/citations/28270508 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28270508 |
| http://purl.uniprot.org/citations/28270508 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28270508 |
| http://purl.uniprot.org/uniprot/#_B2R6P3-mappedCitation-28270508 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270508 |
| http://purl.uniprot.org/uniprot/#_K4RH61-mappedCitation-28270508 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270508 |
| http://purl.uniprot.org/uniprot/#_P50281-mappedCitation-28270508 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270508 |
| http://purl.uniprot.org/uniprot/#_Q16832-mappedCitation-28270508 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270508 |
| http://purl.uniprot.org/uniprot/#_Q5J7V3-mappedCitation-28270508 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270508 |
| http://purl.uniprot.org/uniprot/#_Q6MZT2-mappedCitation-28270508 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270508 |
| http://purl.uniprot.org/uniprot/#_Q8IXG1-mappedCitation-28270508 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270508 |
| http://purl.uniprot.org/uniprot/#_Q9UHK5-mappedCitation-28270508 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270508 |
| http://purl.uniprot.org/uniprot/B2R6P3 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28270508 |
| http://purl.uniprot.org/uniprot/Q8IXG1 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28270508 |