Common signaling pathway is used by the trans-interaction of Necl-5/Tage4/PVR/CD155 and nectin, and of nectin and nectin during the formation of cell-cell adhesion
Common signaling pathway is used by the trans-interaction of Necl-5/Tage4/PVR/CD155 and nectin, and of nectin and nectin during the formation of cell-cell adhesion
复制标题
DOI：
10.1111/j.1349-7006.2005.00087.x
复制
发表时间：
2005-09-01
期刊：
影响因子：
5.7
通讯作者：
Takai, Y
中科院分区：
文献类型：
--
作者：
Sato, T;Irie, K;Takai, Y
Nectin 是一种不依赖 Ca2+ 的 Ig 样细胞间粘附分子，可形成同型和异型反式二聚体（反式相互作用）。 Nectin首先形成细胞间粘附，然后将钙粘蛋白招募到基于Nectin的细胞间粘附位点，与钙粘蛋白协同形成AJ。此外，Nectin与Nectin的反式相互作用诱导Cdc42和Rac小G蛋白的激活，从而增强AJ的形成。通过 nectin 和 nectin 的反式相互作用激活 Cdc42 和 Rac，是由 c-Src、另一种小 G 蛋白 Rap1、Cdc42-GEF、FRG 和 Rac-GEF、Vav2 介导的。 Necl-5/Tage4/PVR/CD155 是另一种不依赖 Ca2+ 的 Ig 样分子，它不与 nectin 家族成员之一的 nectin-3 发生同亲反式相互作用，但发生异嗜反式相互作用。我们在此表明 Necl-5 和 nectin-3 的反式相互作用双向诱导 Cdc42 和 Rac 的激活。与通过 nectin 和 nectin 的反式相互作用激活 Cdc42 和 Rac 类似，Necl-5 和 nectin-3 的反式相互作用首先在基于 Necl-5/nectin-3 的细胞-细胞接触位点招募并激活 c-Src。然后，c-Src 磷酸化 FRG 和 Vav2，酪氨酸磷酸化的 FRG 和 Vav2 被招募到基于 Necl-5/nectin3 的细胞-细胞接触位点。 Necks 和 nectin-3 的反式相互作用还通过 C3G（一种 Rap-GEF）激活 Rap1，并且 Rap1 的这种激活是 Cdc42 和 Rac 激活所必需的。这些结果表明，Necl-5 和 nectin-3 以及 nectin 和 nectin 的反式相互作用通过常见信号分子 c-Src、Rap1、FRG 和 Vav2 诱导 Cdc42 和 Rac 的激活。
Nectin is a Ca2+-independent Ig-like cell-cell adhesion molecule that forms homo- and hetero-trans-dimers (trans- interaction). Nectin first forms cell-cell adhesions and then recruits cadherin to the nectin-based cell-cell adhesion sites to form AJ cooperatively with cadherin. in addition, the trans-interaction of nectin and nectin induces the activation of Cdc42 and Rac small G proteins, which enhances the formation of AJ. The activation of Cdc42 and Rac by the trans-interaction of nectin and nectin is mediated by c-Src, another small G protein, Rap1, a Cdc42-GEF, FRG, and a Rac-GEF, Vav2. Necl-5/Tage4/PVR/CD155 is another Ca2+-independent Ig-like molecule, which does not homophilically trans-interact, but heterophilically trans-interacts with nectin-3, one member of the nectin family. We show here that the trans-interaction of Necl-5 and nectin-3 bidirectionally induces the activation of Cdc42 and Rac. Similarly to the activation of Cdc42 and Rac by the trans- interaction of nectin and nectin, the trans- interaction of Necl-5 and nectin-3 first recruits and activates c-Src at the Necl-5/nectin-3-based cell-cell contact sites. c-Src then phosphorylates FRG and Vav2, and the tyrosine-phosphorylated FRG and Vav2 are recruited to the Necl-5/nectin3-based cell-cell contact sites. The trans-interaction of Necks and nectin-3 also activates Rap1 through C3G, a Rap-GEF, and this activation of Rap1 is required for the activation of Cdc42 and Rac. These results indicate that the trans-interactions of Necl-5 and nectin-3 and of nectin and nectin induce the activation of Cdc42 and Rac through the common signaling molecules c-Src, Rap1, FRG, and Vav2.