Involvement of integrin-induced activation of protein kinase C in the formation of adherens junctions
Involvement of integrin-induced activation of protein kinase C in the formation of adherens junctions
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DOI：
10.1111/j.1365-2443.2007.01083.x
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发表时间：
2007-05-01
期刊：
影响因子：
2.1
通讯作者：
Takai, Yoshimi
中科院分区：
文献类型：
--
作者：
Ozaki, Misa;Ogita, Hisakazu;Takai, Yoshimi
在上皮细胞中，紧密连接(TJ)和粘连连接(AJ)形成连接复合体。在AJ，钙粘附素和胶粘素是主要的细胞-细胞黏附分子。Nectins首先形成细胞-细胞黏附，然后在整合素α(V)β(3)的激活下，将钙粘附素募集到基于Nextin的细胞-细胞黏附部位，形成AJs，然后形成TJs。我们先前的研究表明，当低钙预培养的MDCK细胞用蛋白激酶C(PKC)激活剂12-O-十四酰佛波醇-13-醋酸酯(TPA)处理时，可以得到不完整的AJ和类TJ结构。然而，目前还不清楚PKC是如何被激活的，以及它是如何调节细胞间连接的形成的。低钙预培养的MDCK细胞经TPA处理后，未见整合素α(V)β(3)的激活，可形成不完全的AJs。用TPA处理细胞后，FAK的磷酸化也增强，FAK由外向内传递整合素信号，在Nextin诱导的AJs的形成中发挥作用。此外，抑制PKC也抑制了AJs的形成。这些结果表明，PKC的激活在整合素α(V)β(3)下游和FAK的上游发挥作用，并在Nectin诱导的AJs的形成中起重要作用。
In epithelial cells, tight junctions (TJs) and adherens junctions (AJs) form junctional complexes. At AJs, cadherins and nectins are the major cell-cell adhesion molecules. Nectins first form cell-cell adhesions and then recruit cadherins to the nectin-based cell-cell adhesion sites to form AJs in coordination with the activation of integrin alpha(v)beta(3), followed by the formation of TJs. We previously demonstrated that when MDCK cells precultured at a low Ca2+ concentration were treated with the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA), incomplete AJs and a TJ-like structure were achieved. However, it remains unknown how PKC is activated and how it regulates the formation of cell-cell junctions. When MDCK cells precultured at a low Ca2+ concentration were treated with TPA, incomplete AJs were formed without the activation of integrin alpha(v)beta(3). Treatment of cells with TPA also enhanced the phosphorylation of FAK, which transmits the outside-in signal of integrin and plays a role in the nectin-induced formation of AJs. In addition, inhibition of PKC suppressed the formation of AJs. These results indicate that the activation of PKC functions downstream of integrin alpha(v)beta(3) and upstream of FAK, and is important for the nectin-induced formation of AJs.