| pubmed-article:17245433 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17245433 | lifeskim:mentions | umls-concept:C1155046 | lld:lifeskim |
| pubmed-article:17245433 | lifeskim:mentions | umls-concept:C0025543 | lld:lifeskim |
| pubmed-article:17245433 | lifeskim:mentions | umls-concept:C0542341 | lld:lifeskim |
| pubmed-article:17245433 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:17245433 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:17245433 | pubmed:dateCreated | 2007-1-24 | lld:pubmed |
| pubmed-article:17245433 | pubmed:abstractText | Tight control of T-cell proliferation and effector function is essential to ensure an effective but appropriate immune response. Here, we reveal that this is controlled by the metalloprotease-mediated cleavage of LAG-3, a negative regulatory protein expressed by all activated T cells. We show that LAG-3 cleavage is mediated by two transmembrane metalloproteases, ADAM10 and ADAM17, with the activity of both modulated by two distinct T-cell receptor (TCR) signaling-dependent mechanisms. ADAM10 mediates constitutive LAG-3 cleavage but increases approximately 12-fold following T-cell activation, whereas LAG-3 shedding by ADAM17 is induced by TCR signaling in a PKCtheta-dependent manner. LAG-3 must be cleaved from the cell surface to allow for normal T-cell activation as noncleavable LAG-3 mutants prevented proliferation and cytokine production. Lastly, ADAM10 knockdown reduced wild-type but not LAG-3(-/-) T-cell proliferation. These data demonstrate that LAG-3 must be cleaved to allow efficient T-cell proliferation and cytokine production and establish a novel paradigm in which T-cell expansion and function are regulated by metalloprotease cleavage with LAG-3 as its sole molecular target. | lld:pubmed |
| pubmed-article:17245433 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17245433 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17245433 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17245433 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17245433 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:17245433 | pubmed:issn | 0261-4189 | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:SaftigPaulP | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:BlackRoy ARA | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:WangYaoY | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:BlobelCarl... | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:ForbesKarenK | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:LiNianyuN | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:DempseyPeter... | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:VignaliKate... | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:VignaliDario... | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:WorkmanCreg... | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:RossiJohn JJJ | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:HartmannDiete... | lld:pubmed |
| pubmed-article:17245433 | pubmed:author | pubmed-author:HealeBret SBS | lld:pubmed |
| pubmed-article:17245433 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17245433 | pubmed:day | 24 | lld:pubmed |
| pubmed-article:17245433 | pubmed:volume | 26 | lld:pubmed |
| pubmed-article:17245433 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17245433 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17245433 | pubmed:pagination | 494-504 | lld:pubmed |
| pubmed-article:17245433 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
