Focal adhesion kinase regulates cell-cell contact formation in epithelial cells via modulation of Rho.
Focal adhesion kinase regulates cell-cell contact formation in epithelial cells via modulation of Rho.
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DOI：
10.1016/j.yexcr.2008.08.010
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发表时间：
2008-10-15
影响因子：
3.7
通讯作者：
Schaller, Michael D.
中科院分区：
文献类型：
--
作者：
Playford, Martin P.;Vadali, Kavita;Cai, Xinming;Burridge, Keith;Schaller, Michael D.
粘着斑激酶（FAK）是一种非受体酪氨酸激酶，在细胞粘附、迁移、增殖和存活等细胞过程中起关键作用。最近的研究还表明FAK参与了细胞间粘附的调节。在这里，证据表明，siRNA介导的抑制FAK水平在NBT-II细胞和显性负突变体的FAK的表达引起的上皮细胞形态的损失，并抑制细胞间粘附的形成。Rac和Rho参与细胞-细胞粘附的调节，并且可以通过FAK信号传导来调节。NBT-II细胞中活性Rac或Rho的表达破坏了细胞-细胞接触的形成，从而促进了与FAK耗尽细胞相似的表型。在FAK耗尽的细胞中，细胞间接触的丧失在显性负性Rho突变体而非显性负性Rac突变体的表达后被阻止。抑制FAK可降低p190 RhoGAP的酪氨酸磷酸化水平，升高GTP结合的Rho水平。这表明FAK通过调节Rho来调节细胞-细胞接触形成。
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase that plays a key role in cellular processes such as cell adhesion, migration, proliferation and survival. Recent studies have also implicated FAK in the regulation of cell-cell adhesion. Here, evidence is presented showing that siRNA-mediated suppression of FAK levels in NBT-II cells and expression of dominant negative mutants of FAK caused loss of epithelial cell morphology and inhibited the formation of cell-cell adhesions. Rac and Rho have been implicated in the regulation of cell-cell adhesions and can be regulated by FAK signaling. Expression of active Rac or Rho in NBT-II cells disrupted formation of cell-cell contacts, thus promoting a phenotype similar to FAK-depleted cells. The loss of intercellular contacts in FAK-depleted cells is prevented upon expression of a dominant negative Rho mutant, but not a dominant negative Rac mutant. Inhibition of FAK decreased tyrosine phosphorylation of p190RhoGAP and elevated the level of GTP-bound Rho. This suggests that FAK regulates cell-cell contact formation by regulation of Rho.
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影响因子：
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