TGF-beta1 induces rearrangement of FLK-1-VE-cadherin-beta-catenin complex at the adherens junction through VEGF-mediated signaling.
TGF-beta1 induces rearrangement of FLK-1-VE-cadherin-beta-catenin complex at the adherens junction through VEGF-mediated signaling.
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DOI：
10.1002/jcb.21935
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发表时间：
2008-12-15
影响因子：
4
通讯作者：
Mignatti, Paolo
中科院分区：
文献类型：
--
作者：
Cook, Brandoch D.;Ferrari, Giovanni;Pintucci, Giuseppe;Mignatti, Paolo
VEGF和TGF-β1诱导血管生成，但对血管内皮细胞的作用相反：VEGF促进存活；TGF-β1诱导细胞凋亡。我们之前的研究表明，TGF-β1通过上调VEGF表达，并通过VEGF受体-2 （flk-1）激活信号传导，诱导内皮细胞凋亡。在TGF-β1的作用下，VEGF信号从生存信号瞬间转化为凋亡信号。VEGF促进细胞存活的部分机制是通过激活PI3K/Akt，其机制依赖于多蛋白复合物的形成，包括flk-1和粘附连接蛋白VE-cadherin和β-catenin。本文报道TGF-β1通过将flk-1与VE-cadherin分离，并增加β-catenin与flk-1和VE-cadherin的结合，诱导粘附体连接复合体重排。这种重排既不是由粘附体连接mRNA或蛋白表达的变化引起的，也不是由翻译后修饰引起的，需要通过flk-1介导VEGF信号传导。这些结果表明，粘附连接是内皮细胞中TGF-β1-VEGF相互作用的重要调控成分。
VEGF and TGF-β1 induce angiogenesis but have opposing effects on vascular endothelial cells: VEGF promotes survival; TGF-β1 induces apoptosis. We have previously shown that TGF-β1 induces endothelial cell apoptosis via up-regulation of VEGF expression and activation of signaling through VEGF receptor-2 (flk-1). In context with TGF-β1, VEGF signaling is transiently converted from a survival into an apoptotic one. VEGF promotes cell survival in part via activation of PI3K/Akt by a mechanism dependent on the formation of a multi-protein complex that includes flk-1 and the adherens junction proteins VE-cadherin and β-catenin. Here we report that TGF-β1 induces rearrangement of the adherens junction complex by separating flk-1 from VE-cadherin and increasing β-catenin association with both flk-1 and VE-cadherin. This rearrangement is caused neither by changes in adherens junction mRNA or protein expression nor by post-translational modification, and requires VEGF signaling through flk-1. These results show that the adherens junction is an important regulatory component of TGF-β1-VEGF interaction in endothelial cells.
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血管内皮钙粘蛋白控制着细胞内室的VEGFR-2内在化和信号传导。
影响因子：
7.8
作者：
Lampugnani, Maria Grazia;Orsenigo, Fabrizio;Gagliani, Maria Cristina;Tacchetti, Carlo;Dejana, Elisabetta
通讯作者：
Dejana, Elisabetta
DOI：
10.1073/pnas.76.10.5217
发表时间：
1979-01-01
影响因子：
11.1
作者：
FOLKMAN, J;HAUDENSCHILD, CC;ZETTER, BR
通讯作者：
ZETTER, BR
影响因子：
56.9
作者：
KECK, PJ;HAUSER, SD;CONNOLLY, DT
通讯作者：
CONNOLLY, DT
影响因子：
3.8
作者：
Hyman, KM;Seghezzi, G;Mignatti, P
通讯作者：
Mignatti, P
影响因子：
3.5
作者：
Ali, Nermin;Yoshizumi, Masanori;Tamaki, Toshiaki
通讯作者：
Tamaki, Toshiaki