Matches in SemOpenAlex for { <https://semopenalex.org/work/W2802261344> ?p ?o ?g. }
- W2802261344 endingPage "8613" @default.
- W2802261344 startingPage "8600" @default.
- W2802261344 abstract "The plasminogen system is essential for dissolution of fibrin clots, and in addition, it is involved in a wide variety of other physiological processes, including proteolytic activation of growth factors, cell migration, and removal of protein aggregates. On the other hand, uncontrolled plasminogen activation contributes to many pathological processes (e.g. tumor cells' invasion in cancer progression). Moreover, some virulent bacterial species (e.g. Streptococci or Borrelia) bind human plasminogen and hijack the host's plasminogen system to penetrate tissue barriers. Thus, the conversion of plasminogen to the active serine protease plasmin must be tightly regulated. Here, we show that human lactoferrin, an iron-binding milk glycoprotein, blocks plasminogen activation on the cell surface by direct binding to human plasminogen. We mapped the mutual binding sites to the N-terminal region of lactoferrin, encompassed also in the bioactive peptide lactoferricin, and kringle 5 of plasminogen. Finally, lactoferrin blocked tumor cell invasion in vitro and also plasminogen activation driven by Borrelia. Our results explain many diverse biological properties of lactoferrin and also suggest that lactoferrin may be useful as a potential tool for therapeutic interventions to prevent both invasive malignant cells and virulent bacteria from penetrating host tissues. The plasminogen system is essential for dissolution of fibrin clots, and in addition, it is involved in a wide variety of other physiological processes, including proteolytic activation of growth factors, cell migration, and removal of protein aggregates. On the other hand, uncontrolled plasminogen activation contributes to many pathological processes (e.g. tumor cells' invasion in cancer progression). Moreover, some virulent bacterial species (e.g. Streptococci or Borrelia) bind human plasminogen and hijack the host's plasminogen system to penetrate tissue barriers. Thus, the conversion of plasminogen to the active serine protease plasmin must be tightly regulated. Here, we show that human lactoferrin, an iron-binding milk glycoprotein, blocks plasminogen activation on the cell surface by direct binding to human plasminogen. We mapped the mutual binding sites to the N-terminal region of lactoferrin, encompassed also in the bioactive peptide lactoferricin, and kringle 5 of plasminogen. Finally, lactoferrin blocked tumor cell invasion in vitro and also plasminogen activation driven by Borrelia. Our results explain many diverse biological properties of lactoferrin and also suggest that lactoferrin may be useful as a potential tool for therapeutic interventions to prevent both invasive malignant cells and virulent bacteria from penetrating host tissues." @default.
- W2802261344 created "2018-05-17" @default.
- W2802261344 creator A5009572805 @default.
- W2802261344 creator A5012058569 @default.
- W2802261344 creator A5013844266 @default.
- W2802261344 creator A5015744633 @default.
- W2802261344 creator A5021705820 @default.
- W2802261344 creator A5026768848 @default.
- W2802261344 creator A5029384317 @default.
- W2802261344 creator A5044043152 @default.
- W2802261344 creator A5052506614 @default.
- W2802261344 creator A5057095426 @default.
- W2802261344 creator A5079726873 @default.
- W2802261344 creator A5084552272 @default.
- W2802261344 date "2018-06-01" @default.
- W2802261344 modified "2023-10-16" @default.
- W2802261344 title "Lactoferrin is a natural inhibitor of plasminogen activation" @default.
- W2802261344 cites W1519118220 @default.
- W2802261344 cites W1606739417 @default.
- W2802261344 cites W1636745306 @default.
- W2802261344 cites W16631805 @default.
- W2802261344 cites W1949825747 @default.
- W2802261344 cites W1966227643 @default.
- W2802261344 cites W1968529627 @default.
- W2802261344 cites W1971065280 @default.
- W2802261344 cites W1975926865 @default.
- W2802261344 cites W1977914700 @default.
- W2802261344 cites W1980173932 @default.
- W2802261344 cites W1982066606 @default.
- W2802261344 cites W1988015362 @default.
- W2802261344 cites W2001432760 @default.
- W2802261344 cites W2003738391 @default.
- W2802261344 cites W2010801138 @default.
- W2802261344 cites W2011183875 @default.
- W2802261344 cites W2011784685 @default.
- W2802261344 cites W2018406366 @default.
- W2802261344 cites W201928681 @default.
- W2802261344 cites W2020714594 @default.
- W2802261344 cites W2031216446 @default.
- W2802261344 cites W2032325397 @default.
- W2802261344 cites W2035591620 @default.
- W2802261344 cites W2039053151 @default.
- W2802261344 cites W2041525443 @default.
- W2802261344 cites W2050300060 @default.
- W2802261344 cites W2052881431 @default.
- W2802261344 cites W2058239698 @default.
- W2802261344 cites W2065791048 @default.
- W2802261344 cites W2070794111 @default.
- W2802261344 cites W2076108540 @default.
- W2802261344 cites W2078129398 @default.
- W2802261344 cites W2085429393 @default.
- W2802261344 cites W2099766722 @default.
- W2802261344 cites W2103064512 @default.
- W2802261344 cites W2115451817 @default.
- W2802261344 cites W2120893830 @default.
- W2802261344 cites W2121141343 @default.
- W2802261344 cites W2124757569 @default.
- W2802261344 cites W2127395738 @default.
- W2802261344 cites W2128380267 @default.
- W2802261344 cites W2130479394 @default.
- W2802261344 cites W2134711129 @default.
- W2802261344 cites W2140186583 @default.
- W2802261344 cites W2142137010 @default.
- W2802261344 cites W2143486607 @default.
- W2802261344 cites W2157003645 @default.
- W2802261344 cites W2167361397 @default.
- W2802261344 cites W2300961054 @default.
- W2802261344 cites W2323347146 @default.
- W2802261344 cites W2396485130 @default.
- W2802261344 cites W2396729639 @default.
- W2802261344 cites W2400754861 @default.
- W2802261344 cites W4027862 @default.
- W2802261344 cites W4246370983 @default.
- W2802261344 cites W43302742 @default.
- W2802261344 cites W4379250858 @default.
- W2802261344 cites W74915632 @default.
- W2802261344 doi "https://doi.org/10.1074/jbc.ra118.003145" @default.
- W2802261344 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5986228" @default.
- W2802261344 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29669808" @default.
- W2802261344 hasPublicationYear "2018" @default.
- W2802261344 type Work @default.
- W2802261344 sameAs 2802261344 @default.
- W2802261344 citedByCount "31" @default.
- W2802261344 countsByYear W28022613442018 @default.
- W2802261344 countsByYear W28022613442019 @default.
- W2802261344 countsByYear W28022613442020 @default.
- W2802261344 countsByYear W28022613442021 @default.
- W2802261344 countsByYear W28022613442022 @default.
- W2802261344 countsByYear W28022613442023 @default.
- W2802261344 crossrefType "journal-article" @default.
- W2802261344 hasAuthorship W2802261344A5009572805 @default.
- W2802261344 hasAuthorship W2802261344A5012058569 @default.
- W2802261344 hasAuthorship W2802261344A5013844266 @default.
- W2802261344 hasAuthorship W2802261344A5015744633 @default.
- W2802261344 hasAuthorship W2802261344A5021705820 @default.
- W2802261344 hasAuthorship W2802261344A5026768848 @default.
- W2802261344 hasAuthorship W2802261344A5029384317 @default.
- W2802261344 hasAuthorship W2802261344A5044043152 @default.