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

Hic-5是局灶黏附复合体的一个组成部分，参与整合素引发的信号调节。在成纤维细胞中，Hie5被发现与paxillin竞争局灶黏附激酶（FAK），从而抑制细胞的扩散和运动。这种抑制是通过v-Src的过表达或Raci的组成活性形式来恢复的。这些结果表明Hie5阻断局灶黏附的整合素信号并调节下游信号通路。另一方面，hicc -5在氧化应激下易位至细胞核。Hic-5在其n端LD3结构域含有核排斥信号，以及参与核易位的氧化还原敏感半胱氨酸残基。在细胞核中，Hic-5似乎调节了几个靶基因如c-fos和p21的转录。在报告分析中，Hic-5通过激活Sp1元素刺激c-los增强子。没有检测到Hic-5与Spi之间的直接关联，但Hic-5与Smad3形成复合物，参与TGF*-信号素。因此，Hic-5不仅参与表面信号传导，还参与细胞核转录调控。

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.