{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:09:25Z","timestamp":1791400165983,"version":"4.3.3"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1992,8,15]]},"abstract":"<jats:p>Tissue-type plasminogen activator (t-PA), a serine protease that catalyzes the initial and rate-limiting step in the fibrinolytic cascade, is cleared rapidly in vivo by the liver. Using chemical crosslinking, we have recently identified a plasminogen-activator inhibitor type 1 (PAI-1)-independent t-PA clearance receptor on rat hepatoma MH1C1 cells with a relative molecular mass of approximately 500 kDa. Another recently identified membrane receptor, low density lipoprotein receptor-related protein\/alpha 2-macroglobulin receptor (LRP\/alpha 2MR), was also detected on MH1C1 hepatoma cells by using immunoprecipitation with anti-LRP\/alpha 2MR antibody. When analyzed by SDS\/PAGE, we found the t-PA receptor identified on MH1C1 cells comigrated with the large subunit of LRP\/alpha 2MR. The t-PA receptor was immunoprecipitated by an anti-LRP\/alpha 2MR antibody after chemical crosslinking of specifically bound 125I-labeled t-PA to its receptor. Through chemical crosslinking studies, we found that t-PA and methylamine-activated alpha 2-macroglobulin could bind to LRP\/alpha 2MR simultaneously without competing with one another for binding, suggesting that the two ligands bound to two independent sites on the LRP\/alpha 2MR molecule. Furthermore, a 39-kDa protein, which modulates ligand binding to LRP\/alpha 2MR, was also found to inhibit t-PA binding to its receptor. These data thus show that the t-PA clearance receptor identified on MH1C1 hepatoma cells is LRP\/alpha 2MR.<\/jats:p>","DOI":"10.1073\/pnas.89.16.7427","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:05:55Z","timestamp":1149062755000},"page":"7427-7431","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":257,"title":["Low density lipoprotein receptor-related protein\/alpha 2-macroglobulin receptor is an hepatic receptor for tissue-type plasminogen activator."],"prefix":"10.1073","volume":"89","author":[{"given":"G","family":"Bu","sequence":"first","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Williams","sequence":"additional","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D K","family":"Strickland","sequence":"additional","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A L","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1992,8,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.89.16.7427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:04:30Z","timestamp":1649855070000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.89.16.7427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,8,15]]},"references-count":0,"journal-issue":{"issue":"16","published-print":{"date-parts":[[1992,8,15]]}},"alternative-id":["10.1073\/pnas.89.16.7427"],"URL":"https:\/\/doi.org\/10.1073\/pnas.89.16.7427","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,8,15]]},"assertion":[{"value":"1992-08-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}