Department of Structural Analysis, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Histol Histopathol. 2010 Mar;25(3):387-96. doi: 10.14670/HH-25.387.
Angiopoietin (Ang) 1 is a ligand for endothelium-specific receptor tyrosine kinase Tie-2. In adult vasculature, Ang1/Tie2 signaling is thought to regulate both maintenance of vascular quiescence and promotion of angiogenesis. However, it has been unknown how Tie2 signal regulates these distinct biological functions. Recently, we and Alitalo's group have clarified that Ang1 assembles distinct Tie2 signaling complexes in either presence or absence of endothelial cell-cell adhesions. Ang1 induces trans-association of Tie2 at cell-cell contacts, whereas Tie2 is anchored to the extracellular matrix (ECM) by Ang1 at the cell-substratum interface. Trans-associated Tie2 and ECM-anchored Tie2 activate distinct signaling pathways. In this review, we discuss how Ang1/Tie2 signal regulates both maintenance of vascular quiescence and promotion of angiogenesis, especially focusing on the roles of trans-associated Tie2 and ECM-anchored Tie2.
血管生成素 (Ang) 1 是内皮细胞特异性受体酪氨酸激酶 Tie-2 的配体。在成人脉管系统中，Ang1/Tie2 信号被认为调节血管静止的维持和血管生成的促进。然而，Tie2 信号如何调节这些不同的生物学功能尚不清楚。最近，我们和 Alitalo 的小组已经阐明，Ang1 在存在或不存在内皮细胞-细胞黏附的情况下组装不同的 Tie2 信号复合物。Ang1 在细胞-细胞连接处诱导 Tie2 的跨关联，而 Tie2 通过 Ang1 在细胞-基质界面处锚定到细胞外基质 (ECM)。跨关联的 Tie2 和 ECM 锚定的 Tie2 激活不同的信号通路。在这篇综述中，我们讨论了 Ang1/Tie2 信号如何调节血管静止的维持和血管生成的促进，特别是关注跨关联的 Tie2 和 ECM 锚定的 Tie2 的作用。
