biostudies-literatureUnknown122(6)Felcht MAngiopoietin-2 (ANG-2) is a key regulator of angiogenesis that exerts context-dependent effects on ECs. ANG-2 binds the endothelial-specific receptor tyrosine kinase 2 (TIE2) and acts as a negative regulator of ANG-1/TIE2 signaling during angiogenesis, thereby controlling the responsiveness of ECs to exogenous cytokines. Recent data from tumors indicate that under certain conditions ANG-2 can also promote angiogenesis. However, the molecular mechanisms of dual ANG-2 functions are poorly understood. Here, we identify a model for the opposing roles of ANG-2 in angiogenesis. We found that angiogenesis-activated endothelium harbored a subpopulation of TIE2-negative ECs (TIE2lo). TIE2 expression was downregulated in angiogenic ECs, which abundantly expressed several integrins. ANG-2 bound to thThe Journal of clinical investigation1991-2005https://www.ebi.ac.uk/biostudies/studies/S-EPMC3366398biostudies-literatureAngiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling.PMC3366398Besemfelder EChavakis EKutschera SSchering AVettel CKienast YLoos EKLuck RTerhardt DGoerdt SBartels SSeidel PKlein CThomas MHu JAppak SBartol AUemura AFelcht MSrivastava KWieland TAugustin HGfalseAngiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling.Angiopoietin-2 (ANG-2) is a key regulator of angiogenesis that exerts context-dependent effects on ECs. ANG-2 binds the endothelial-specific receptor tyrosine kinase 2 (TIE2) and acts as a negative regulator of ANG-1/TIE2 signaling during angiogenesis, thereby controlling the responsiveness of ECs to exogenous cytokines. Recent data from tumors indicate that under certain conditions ANG-2 can also promote angiogenesis. However, the molecular mechanisms of dual ANG-2 functions are poorly understood. Here, we identify a model for the opposing roles of ANG-2 in angiogenesis. We found that angiogenesis-activated endothelium harbored a subpopulation of TIE2-negative ECs (TIE2lo). TIE2 expression was downregulated in angiogenic ECs, which abundantly expressed several integrins. ANG-2 bound to th2012-01-01T00:00:00Z2012 Jun2025-04-03T22:33:47.57Z2019-03-27T00:54:07ZS-EPMC33663982258557610.1172/JCI5883210.1172/jci58832