Regulation of adhesion signals by a focal adhesion protein, Hie5.

HIC-5是粘着斑复合体的一个组成部分，参与整合素信号的调节。在成纤维细胞中，Hie5被发现与巴西林竞争粘着斑激酶(FAK)，从而抑制细胞的扩散和运动。这种抑制被恢复到v-Src或构成活性形式的Raci的过度表达。这些结果表明，Hie5在粘着斑处阻断整合素信号，并调节下游信号通路。另一方面，Hic-5在氧化应激下移位到细胞核。HIC-5在其N端的LD3区域含有核排斥信号，以及参与核转位的氧化还原敏感的半胱氨酸残基。在细胞核内，Hic-5似乎调节c-fos和p21等靶基因的转录。在报告实验中，Hic-5通过激活Sp1元件来激活c-LOS增强子。未检测到Hic-5与Spi之间的直接联系，但Hic-5与Smad3形成了参与转化生长因子信号转导的复合体。因此，Hic-5不仅参与表面信号转导，还参与核转录调控。

Hic-5 is a component of the focal adhesion complex, and is involved in regulation of signaling elicited from integrins. In fibroblastic cells, Hie5 was found to compete focal adhesion kinase (FAK) with paxillin, thereby inhibited cell spreading and motility. This inhibition was restored yb overexpression of v-Src or constitutive active form of Raci. These results indicate that Hie5 blocks integrin signals at the focal adhesion and regulates downstream signaling pathways. On the other hand, Hic-5 translocated to the nucleus under oxidative stress. Hic-5 contains nuclear exclusion signal in its N-terminal LD3 domain, and redox-sensitive cystein residues that participate in the nuclear translocation. In the nucleus, Hic-5 seemed to regulate transcription of several target genes such as c-fos and p21.In reporter assays, Hic-5 stimulated c-los enhancer through activation of Sp1 elements. Direct association between Hic-5 and Spi was not detected, but Hic-5 formed a complex with Smad3 that is involved in TGF*-signalin. Thus, Hic-5 participates not only in the surface signaling, but also in the nuclear transcriptional regulation.