| pubmed-article:21041295 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21041295 | lifeskim:mentions | umls-concept:C0019143 | lld:lifeskim |
| pubmed-article:21041295 | lifeskim:mentions | umls-concept:C1150182 | lld:lifeskim |
| pubmed-article:21041295 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:21041295 | pubmed:issue | 53 | lld:pubmed |
| pubmed-article:21041295 | pubmed:dateCreated | 2010-12-27 | lld:pubmed |
| pubmed-article:21041295 | pubmed:abstractText | Like most metalloproteases, matrix metalloprotease 2 (MMP-2) is synthesized as a zymogen. MMP-2 propeptide plays a role in inhibition of catalytic activity through a cysteine-zinc ion pairing, disruption of which results in full enzyme activation. A variety of proteases have been shown to be involved in the activation of pro-MMP-2, including metalloproteases and serine proteases. In the previous study we showed that MMP-2 activation occurred via specific cleavages of the propeptide by thrombin followed by intermolecular autoproteolytic processing for full enzymatic activity. Thrombin also degraded MMP-2, but this degradation was reduced greatly under cell-associated conditions with a concomitant increase in activation, prompting us to elucidate the molecular mechanisms underlying thrombin-mediated MMP-2 activation. In the present study we demonstrate that heparan sulfate is essential for thrombin-mediated activation of pro-MMP-2. Binding of heparan sulfate to thrombin is primarily responsible for this activation process, presumably through conformational changes at the active site. Furthermore, interaction of MMP-2 with exosites 1 and 2 of thrombin is crucial for thrombin-mediated MMP-2 degradation, and inhibition of this interaction by heparan sulfate or hirudin fragment results in a decrease in MMP-2 degradation. Finally, we demonstrated interaction between exosite 1 and hemopexin-like domain of MMP-2, suggesting a regulatory role of hemopexin-like domain in MMP-2 degradation. Taken together, our experimental data suggest a novel regulatory mechanism of thrombin-dependent MMP-2 enzymatic activity by heparan sulfate proteoglycans. | lld:pubmed |
| pubmed-article:21041295 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21041295 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041295 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21041295 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041295 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041295 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041295 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21041295 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21041295 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:21041295 | pubmed:issn | 1083-351X | lld:pubmed |
| pubmed-article:21041295 | pubmed:author | pubmed-author:KimDoo-SikDS | lld:pubmed |
| pubmed-article:21041295 | pubmed:author | pubmed-author:KooBon-HunBH | lld:pubmed |
| pubmed-article:21041295 | pubmed:author | pubmed-author:YeomYoung... | lld:pubmed |
| pubmed-article:21041295 | pubmed:author | pubmed-author:HanJung HoJH | lld:pubmed |
| pubmed-article:21041295 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21041295 | pubmed:day | 31 | lld:pubmed |
| pubmed-article:21041295 | pubmed:volume | 285 | lld:pubmed |
| pubmed-article:21041295 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21041295 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21041295 | pubmed:pagination | 41270-9 | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:meshHeading | pubmed-meshheading:21041295... | lld:pubmed |
| pubmed-article:21041295 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:21041295 | pubmed:articleTitle | Thrombin-dependent MMP-2 activity is regulated by heparan sulfate. | lld:pubmed |
| pubmed-article:21041295 | pubmed:affiliation | Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea. k4119@yonsei.ac.kr | lld:pubmed |
| pubmed-article:21041295 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21041295 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:4313 | entrezgene:pubmed | pubmed-article:21041295 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:21041295 | lld:entrezgene |
