Involvement of the c-Src-Crk-C3G-Rap1 signaling in the nectin-induced activation of Cdc42 and formation of adherens junctions
Involvement of the c-Src-Crk-C3G-Rap1 signaling in the nectin-induced activation of Cdc42 and formation of adherens junctions
复制标题
DOI：
10.1074/jbc.m411099200
复制
发表时间：
2005-01-07
影响因子：
4.8
通讯作者：
Takai, Y
中科院分区：
文献类型：
--
作者：
Fukuyama, T;Ogita, H;Takai, Y
Nectin是一种钙离子非依赖性免疫球蛋白样细胞间粘附分子，可诱导Cdc 42和Rac小G蛋白的活化，从而促进基于钙粘蛋白的粘附连接（AJs）和基于密蛋白的紧密连接的形成。连接素在基于连接素的细胞-细胞接触位点募集并激活c-Src。c-Src然后通过FRG（Cdc 42-GDP/GTP交换因子）激活Cdc 42。我们发现Rap 1小G蛋白参与了连接素诱导的Cdc 42的激活和AJs的形成。Rap 1被募集到基于连接素的细胞-细胞接触位点，并通过c-Src-Crk-C3 G信号传导在那里局部激活。单独的c-Src或Rap 1的激活对于FRG的激活是不够的，并且这两种分子的激活对于FRG的激活是必需的。Rap 1的激活不是c-Src介导的FRG磷酸化或募集所必需的。Crk、C3 G或Rap 1信号的抑制减少了AJs的形成。这些结果表明Rap 1通过c-Src-Crk-C3 G信号被nectin激活，并参与nectin诱导的、c-Src和FRG介导的Cdc 42激活和AJs形成。
Nectins, Ca2+-independent immunoglobulin-like cell-cell adhesion molecules, induce the activation of Cdc42 and Rac small G proteins, enhancing the formation of cadherin-based adherens junctions (AJs) and claudin-based tight junctions. Nectins recruit and activate c-Src at the nectin-based cell-cell contact sites. c-Src then activates Cdc42 through FRG, a Cdc42-GDP/GTP exchange factor. We showed here that Rap1 small G protein was involved in the nectin-induced activation of Cdc42 and formation of AJs. Rap1 was recruited to the nectin-based cell-cell contact sites and locally activated through the c-Src-Crk-C3G signaling there. The activation of either c-Src or Rap1 alone was insufficient for and the activation of both molecules was essential for the activation of FRG. The activation of Rap1 was not necessary for the c-Src-mediated phosphorylation or recruitment of FRG. The inhibition of the Crk, C3G, or Rap1 signaling reduced the formation of AJs. These results indicate that Rap1 is activated by nectins through the c-Src-Crk-C3G signaling and involved in the nectin-induced, c-Src- and FRG-mediated activation of Cdc42 and formation of AJs.