http://rdf.ncbi.nlm.nih.gov/pubchem/patent/EP-1636251-A2
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_b83b85d7d95293b3fc4ba79112f09941 |
| classificationCPCAdditional | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/G01N2333-705 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/G01N33-5088 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07K14-515 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/G01N33-50 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K38-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07K14-515 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07K- http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C12Q1-00 |
| filingDate | 2004-06-21^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_0a7f8baa6e7320d6097f189569da9066 |
| publicationDate | 2006-03-22^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | EP-1636251-A2 |
| titleOfInvention | Ccn1 compositions and methods |
| abstract | The angiogenic inducer CCN1 (cysteine-rich 61, CYR61), a secreted matricellular protein of the CCN family, is a ligand of multiple integrins including α6β1. Previous studies have shown that CCN1 interaction with integrin α6β1 mediates adhesion of fibroblasts, endothelial cells, and smooth muscle cells, as well as migration of smooth muscle cells. Recently, we have reported that CCN1-induced tubule formation of unactivated endothelial cells is also mediated through integrin α6β1. In this study, we demonstrate that human skin fibroblasts adhere specifically to the T1 sequence (GQKCIVQTTSWSQCSKS) within domain III of CCN1, and this process is blocked by anti-a6 and anti-b1 monoclonal antibodies. Alanine substitution mutagenesis of the T1 sequence further defines the sequence TTSWSQCSKS as the critical determinant for mediating α6β1-dependent adhesion. Soluble T1 peptide specifically inhibits fibroblast adhesion to CCN1 in a dose-dependent manner. Furthermore, T1 also inhibits cell adhesion to other α6β1 ligands including CCN2 (CTGF), CCN3 (NOV), and laminin, but not to ligands of other integrins. In addition, T1 specifically inhibits α6β1-dependent tubule formation of unactivated endothelial cells in a CCN1-containing collagen gel matrix. To confirm that T1 binds integrin α6β1 directly, we perform affinity chromatography and show that integrin α6β1 is isolated from an octylglucoside extract of fibroblasts on T1-coupled Affi-gel. Taken together, these findings define the T1 sequence in CCN1 as a novel binding motif for integrin α6β1, and form the basis for the development of peptide mimetics to examine the functional role of α6β1 in angiogenesis. |
| priorityDate | 2003-06-20^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
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