Cell adhesion regulates the interaction between the docking protein p130Cas and the 14-3-3 proteins
Cell adhesion regulates the interaction between the docking protein p130Cas and the 14-3-3 proteins
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DOI：
10.1074/jbc.274.9.5762
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发表时间：
1999-02-26
影响因子：
4.8
通讯作者：
Vuori, K
中科院分区：
文献类型：
--
作者：
Garcia-Guzman, M;Dolfi, F;Vuori, K
整合素配体结合通过对接蛋白 p130(Cas) (Cas) 与不同分子的直接结合诱导信号传导复合物的形成。我们在此报告，在酵母双杂交测定中，14-3-3 zeta 蛋白与 Cas 相互作用，我们还发现这两种蛋白在哺乳动物细胞中结合，并且这种相互作用以磷酸丝氨酸依赖性方式发生，因为用丝氨酸磷酸酶处理 Cas 大大降低了其结合 14-3-3 zeta 的能力。此外，发现 Cas-14-3-3 zeta 相互作用受到整合素介导的细胞粘附的调节。因此，当细胞与细胞外基质分离时，Cas 与 14-3-3 zeta 的结合大大减弱，而将细胞重新铺到纤连蛋白上会迅速诱导这种结合。与这些结果一致，我们发现Cas和14-3-3的亚细胞定位也受到整联蛋白配体结合的调节，并且这两种蛋白在细胞附着到细胞外基质期间表现出显着的共定位。总之，我们的结果表明，14-3-3 蛋白通过与 Gas 相互作用参与整合素激活的信号通路，这反过来可能有助于细胞粘附到细胞外基质调节的重要生物反应。
Integrin Ligand binding induces a signaling complex formation via the direct association of the docking protein p130(Cas) (Cas) with diverse molecules. We report here that the 14-3-3 zeta protein interacts with Cas in the yeast two-hybrid assay, we also found that the two proteins associate in mammalian cells and that this interaction takes place in a phosphoserine-dependent manner, because treatment of Cas with a serine phosphatase greatly reduced its ability to bind 14-3-3 zeta. Furthermore, the Cas-14-3-3 zeta interaction was found to be regulated by integrin-mediated cell adhesion. Thus, when cells are detached from the extracellular matrix, the binding of Cas to 14-3-3 zeta is greatly diminished, whereas replating the cells onto fibronectin rapidly induces the association. Consistent with these results, we found that the subcellular localization of Cas and 14-3-3 is also regulated by integrin ligand binding and that the two proteins display a significant co-localization during cell attachment to the extracellular matrix. In conclusion, our results demonstrate that 14-3-3 proteins participate in integrin-activated signaling pathways through their interaction with Gas, which, in turn, may contribute to important biological responses regulated by cell adhesion to the extracellular matrix.