Activation of Cdc42 by trans interactions of the cell adhesion molecules nectins through c-Src and Cdc42-GEF FRG.

Activation of Cdc42 by trans interactions of the cell adhesion molecules nectins through c-Src and Cdc42-GEF FRG.
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DOI:
10.1083/jcb.200401093
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发表时间:
2004-08-02
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Takai Y
Takai Y
中科院分区:
其他
文献类型:
--
作者:
Fukuhara T;Shimizu K;Kawakatsu T;Fukuyama T;Minami Y;Honda T;Hoshino T;Yamada T;Ogita H;Okada M;Takai Y

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Nectins是一种不依赖于钙离子的免疫球蛋白样细胞-细胞黏附分子,通过其反式相互作用启动细胞-细胞黏附,并招募钙粘附素协同形成黏附连接(AJ)。此外,果胶蛋白的反式相互作用诱导了CDc42和Rac小G蛋白的激活,从而加快了AJ的形成速度。在这里,我们研究了蜜环素如何诱导MDCK上皮细胞和L成纤维细胞中CDC42的激活。Nectins在基于Nectin的细胞-细胞黏附部位募集和激活c-Src。FRG是一种专用于CDC42的GDP/GTP交换因子,然后在那里招募,c-Src将酪氨酸磷酸化并激活,导致CDC42的GTP结合活性形式增加。抑制Nectin诱导的c-Src激活可抑制Nextin诱导的FRG和CDC42的激活。通过RNA干扰抑制Nextin诱导的FRG的激活或FRG的耗竭,抑制Nectin诱导的CDc42的激活。这些结果表明,蜜环素通过c-Src和FRG在基于蜜环素的细胞-细胞黏附部位局部诱导CDC42的激活。
Nectins, Ca2+-independent immunoglobulin-like cell–cell adhesion molecules, initiate cell–cell adhesion by their trans interactions and recruit cadherins to cooperatively form adherens junctions (AJs). In addition, the trans interactions of nectins induce the activation of Cdc42 and Rac small G proteins, which increases the velocity of the formation of AJs. We examined here how nectins induce the activation of Cdc42 in MDCK epithelial cells and L fibroblasts. Nectins recruited and activated c-Src at the nectin-based cell–cell adhesion sites. FRG, a GDP/GTP exchange factor specific for Cdc42, was then recruited there, tyrosine phosphorylated by c-Src, and activated, causing an increase in the GTP-bound active form of Cdc42. Inhibition of the nectin-induced activation of c-Src suppressed the nectin-induced activation of FRG and Cdc42. Inhibition of the nectin-induced activation of FRG or depletion of FRG by RNA interference suppressed the nectin-induced activation of Cdc42. These results indicate that nectins induce the activation of Cdc42 through c-Src and FRG locally at the nectin-based cell–cell adhesion sites.
整联蛋白alpha2beta1通过激活SRC激酶和PLCGAMMA2介导胶原蛋白上血小板扩散的外部调节。
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