Involvement of FAK and PTP-PEST in the regulation of redox-sensitive nuclear-cytoplasmic shuttling of a LIM protein, Hic-5
Involvement of FAK and PTP-PEST in the regulation of redox-sensitive nuclear-cytoplasmic shuttling of a LIM protein, Hic-5
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DOI：
10.1089/ars.2005.7.335
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发表时间：
2005-03-01
影响因子：
6.6
通讯作者：
Nose, K
中科院分区：
文献类型：
--
作者：
Shibanuma, M;Mori, K;Nose, K
LIM蛋白Hic-5是一种通过氧化还原敏感的核输出信号穿梭于细胞核内外的粘着斑蛋白，与其他粘着斑蛋白（包括与Hic-5同源性最高的蛋白桩蛋白）不同，LIM蛋白Hic-5在氧化条件下在细胞核中积累，并参与c-fos和p21（cip 1）基因的转录。在这里，我们研究了Hic-5的相互作用伙伴，粘着斑激酶（FAK）和蛋白酪氨酸磷酸酶PEST（PTP-PEST），在Hic-5的核转位的作用，发现它们是抑制性的。有趣的是，Hic-5与FAK的相互作用受结合位点附近的特定半胱氨酸的调节，并且在氧化条件下在细胞中减少。它与PTP-PEST的相互作用对氧化剂也很敏感。这些结果表明，核质穿梭或Hic-5是由其相互作用的合作伙伴在局灶性粘连或在细胞质中的氧化还原敏感的方式进行调节，协调其在局灶性粘连的作用，在细胞核中，这取决于细胞的氧化还原状态。细胞松弛素D或佛波酯还诱导Hic-5的核积聚，而活性氧自由基（ROS）清除剂则抑制Hic-5的核积聚，这表明除了氧化剂外，内源性产生的ROS也诱导Hic-5的核积聚。
The LIM protein Hic-5 is a focal adhesion protein shuttling in and out of the nucleus through the redox-sensitive nuclear export signal, and unlike other focal adhesion proteins including paxillin, the protein most homologous to Hic-5, it accumulates in the nucleus under oxidative conditions and participates in the transcription of c-fos and p21(cip1) genes. Here, we examined the roles of the interacting partners of Hic-5, focal adhesion kinase (FAK) and protein tyrosine phosphatase PEST (PTP-PEST), in the nuclear translocation of Hic-5 and found that they were inhibitory. Interestingly, the interaction of Hic-5 with FAK was regulated by specific cysteines near the binding site and decreased in cells under oxidative conditions. Its interaction with PTP-PEST was also sensitive to the oxidant. These results suggest that the nuclear-cytoplasmic shuttling or Hic-5 is regulated by its interacting partners at focal adhesions or in the cytoplasm in a redox-sensitive manner, coordinating its role at focal adhesions with that in the nucleus, depending on the redox state of cells. Cytochalasin D or a phorbol ester also induced nuclear accumulation of Hic-5, which was inhibited by scavengers of reactive oxygen species (ROS), suggesting that besides oxidants, endogenously produced ROS induced the nuclear accumulation of Hic-5.