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- W2517498730 endingPage "3510" @default.
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- W2517498730 abstract "The angiopoietin/Tie (ANG/Tie) receptor system controls developmental and tumor angiogenesis, inflammatory vascular remodeling, and vessel leakage. ANG1 is a Tie2 agonist that promotes vascular stabilization in inflammation and sepsis, whereas ANG2 is a context-dependent Tie2 agonist or antagonist. A limited understanding of ANG signaling mechanisms and the orphan receptor Tie1 has hindered development of ANG/Tie-targeted therapeutics. Here, we determined that both ANG1 and ANG2 binding to Tie2 increases Tie1-Tie2 interactions in a β1 integrin-dependent manner and that Tie1 regulates ANG-induced Tie2 trafficking in endothelial cells. Endothelial Tie1 was essential for the agonist activity of ANG1 and autocrine ANG2. Deletion of endothelial Tie1 in mice reduced Tie2 phosphorylation and downstream Akt activation, increased FOXO1 nuclear localization and transcriptional activation, and prevented ANG1- and ANG2-induced capillary-to-venous remodeling. However, in acute endotoxemia, the Tie1 ectodomain that is responsible for interaction with Tie2 was rapidly cleaved, ANG1 agonist activity was decreased, and autocrine ANG2 agonist activity was lost, which led to suppression of Tie2 signaling. Tie1 cleavage also occurred in patients with hantavirus infection. These results support a model in which Tie1 directly interacts with Tie2 to promote ANG-induced vascular responses under noninflammatory conditions, whereas in inflammation, Tie1 cleavage contributes to loss of ANG2 agonist activity and vascular stability." @default.
- W2517498730 created "2016-09-16" @default.
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- W2517498730 date "2016-08-22" @default.
- W2517498730 modified "2023-10-17" @default.
- W2517498730 title "Tie1 controls angiopoietin function in vascular remodeling and inflammation" @default.
- W2517498730 cites W135569227 @default.
- W2517498730 cites W1567433779 @default.
- W2517498730 cites W1590306662 @default.
- W2517498730 cites W1758592134 @default.
- W2517498730 cites W1861297546 @default.
- W2517498730 cites W1960983795 @default.
- W2517498730 cites W1964310770 @default.
- W2517498730 cites W1964776939 @default.
- W2517498730 cites W1966821227 @default.
- W2517498730 cites W1970404777 @default.
- W2517498730 cites W1970614272 @default.
- W2517498730 cites W1972344356 @default.
- W2517498730 cites W1973096186 @default.
- W2517498730 cites W1976019207 @default.
- W2517498730 cites W1977721830 @default.
- W2517498730 cites W1978157267 @default.
- W2517498730 cites W1979876108 @default.
- W2517498730 cites W1983089513 @default.
- W2517498730 cites W1985907458 @default.
- W2517498730 cites W1986492410 @default.
- W2517498730 cites W1986774614 @default.
- W2517498730 cites W1993980694 @default.
- W2517498730 cites W1999868932 @default.
- W2517498730 cites W2000440562 @default.
- W2517498730 cites W2005564031 @default.
- W2517498730 cites W2008558555 @default.
- W2517498730 cites W2010671380 @default.
- W2517498730 cites W2031261181 @default.
- W2517498730 cites W2034926252 @default.
- W2517498730 cites W2038968218 @default.
- W2517498730 cites W2042427065 @default.
- W2517498730 cites W2056855407 @default.
- W2517498730 cites W2057280160 @default.
- W2517498730 cites W2059108446 @default.
- W2517498730 cites W2062143592 @default.
- W2517498730 cites W2068506261 @default.
- W2517498730 cites W2077884715 @default.
- W2517498730 cites W2078338839 @default.
- W2517498730 cites W2081596239 @default.
- W2517498730 cites W2082406330 @default.
- W2517498730 cites W2089771697 @default.
- W2517498730 cites W2091915348 @default.
- W2517498730 cites W2094686936 @default.
- W2517498730 cites W2094924608 @default.
- W2517498730 cites W2099298455 @default.
- W2517498730 cites W2100891986 @default.
- W2517498730 cites W2103578762 @default.
- W2517498730 cites W2104679679 @default.
- W2517498730 cites W2115499423 @default.
- W2517498730 cites W2115566079 @default.
- W2517498730 cites W2117743783 @default.
- W2517498730 cites W2119859302 @default.
- W2517498730 cites W2120936045 @default.
- W2517498730 cites W2121717631 @default.
- W2517498730 cites W2126621713 @default.
- W2517498730 cites W2129239355 @default.
- W2517498730 cites W2130986704 @default.
- W2517498730 cites W2134126295 @default.
- W2517498730 cites W2141708447 @default.
- W2517498730 cites W2144776559 @default.
- W2517498730 cites W2149883858 @default.
- W2517498730 cites W2152215024 @default.
- W2517498730 cites W2155160938 @default.
- W2517498730 cites W2157225099 @default.
- W2517498730 cites W2157985193 @default.
- W2517498730 cites W2158473891 @default.
- W2517498730 cites W2160870679 @default.
- W2517498730 cites W2161700314 @default.
- W2517498730 cites W2163301034 @default.
- W2517498730 cites W2165555140 @default.
- W2517498730 cites W2172134293 @default.
- W2517498730 cites W2190979306 @default.
- W2517498730 cites W2212463484 @default.
- W2517498730 cites W2237013884 @default.
- W2517498730 cites W2277373081 @default.
- W2517498730 cites W2296074182 @default.