Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148.
Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148.
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VEGF诱导的增殖的接触抑制需要血管内皮钙粘着蛋白，β-catenin和磷酸酶DEP-1/CD148。
DOI：
10.1083/jcb.200209019
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发表时间：
2003-05-26
影响因子：
7.8
通讯作者：
Dejana, E
中科院分区：
文献类型：
--
作者：
Lampugnani, MG;Zanetti, A;Corada, M;Takahashi, T;Balconi, G;Breviario, F;Orsenigo, F;Cattelino, A;Kemler, R;Daniel, TO;Dejana, E
融合的内皮细胞对VEGF的增殖信号反应较差。比较血管内皮钙粘蛋白（VE-钙粘蛋白）表达不同的同基因内皮细胞，我们发现这种蛋白的存在减弱VEGF诱导的VEGF受体（VEGFR）2酪氨酸磷酸化，p44/p42 MAP激酶磷酸化和细胞增殖。在β-catenin而不是p120结合结构域中截短的VE-钙粘蛋白不能与VEGFR-2结合并诱导其失活。β-连环蛋白缺失的内皮细胞不受VE-钙粘蛋白的接触抑制，并且仍然对VEGF有反应，这表明该蛋白质是抑制生长因子信号传导所必需的。高细胞密度增强PTP 1（DEP-1）//CD 148的显性负突变体以及通过RNA干扰降低其表达部分恢复VEGFR-2磷酸化和MAP激酶活化。总体而言，数据表明VE-钙粘蛋白-β-连环蛋白复合物参与VEGF信号传导的接触抑制。在用VEGF刺激后，VEGFR-2与复合物结合并集中在细胞-细胞接触处，在那里它可能被连接磷酸酶如DEP-1灭活。在稀疏细胞或VE-钙粘蛋白-空细胞中，这种现象不会发生，并且受体被生长因子完全激活。
Confluent endothelial cells respond poorly to the proliferative signals of VEGF. Comparing isogenic endothelial cells differing for vascular endothelial cadherin (VE-cadherin) expression only, we found that the presence of this protein attenuates VEGF-induced VEGF receptor (VEGFR) 2 phosphorylation in tyrosine, p44/p42 MAP kinase phosphorylation, and cell proliferation. VE-cadherin truncated in β-catenin but not p120 binding domain is unable to associate with VEGFR-2 and to induce its inactivation. β-Catenin–null endothelial cells are not contact inhibited by VE-cadherin and are still responsive to VEGF, indicating that this protein is required to restrain growth factor signaling. A dominant-negative mutant of high cell density–enhanced PTP 1 (DEP-1)//CD148 as well as reduction of its expression by RNA interference partially restore VEGFR-2 phosphorylation and MAP kinase activation. Overall the data indicate that VE-cadherin–β-catenin complex participates in contact inhibition of VEGF signaling. Upon stimulation with VEGF, VEGFR-2 associates with the complex and concentrates at cell–cell contacts, where it may be inactivated by junctional phosphatases such as DEP-1. In sparse cells or in VE-cadherin–null cells, this phenomenon cannot occur and the receptor is fully activated by the growth factor.
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影响因子：
8.7
作者：
Balconi, G;Spagnuolo, R;Dejana, E
通讯作者：
Dejana, E
影响因子：
15.9
作者：
Caveda, L;MartinPadura, L;Dejana, E
通讯作者：
Dejana, E
影响因子：
20.3
作者：
Corada, M;Liao, F;Dejana, E
通讯作者：
Dejana, E
DOI：
10.1083/jcb.153.5.1049
发表时间：
2001-05-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gottardi CJ;Wong E;Gumbiner BM
通讯作者：
Gumbiner BM
影响因子：
15.9
作者：
Conacci-Sorrell, M;Zhurinsky, J;Ben-Ze'ev, A
通讯作者：
Ben-Ze'ev, A