Interaction of Hic-5, a senescence-related protein, with focal adhesion kinase
Interaction of Hic-5, a senescence-related protein, with focal adhesion kinase
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DOI：
10.1074/jbc.273.41.26516
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发表时间：
1998-10-09
影响因子：
4.8
通讯作者：
Tachibana, K
中科院分区：
文献类型：
--
作者：
Fujita, H;Kamiguchi, K;Tachibana, K
过氧化氢诱导的克隆(Hic)-5在人成纤维细胞的衰老过程中被诱导，Hic-5的过表达诱导衰老样表型。在结构上，Hic-5与68 kDa的细胞骨架蛋白paxlin具有同源性，如N-末端的LD基序和C-末端的LIM结构域，这里我们证明了Hic-5通过其N-末端结构域与焦点黏附蛋白(FAR)结合，并通过其C-末端LIM结构域定位于焦点黏附。然而，Hic-5既不被COS细胞中共表达的FAK所磷酸化，也不被293T细胞中整合素刺激所磷酸化。此外，Hic-5的过表达导致巴西林的酪氨酸磷酸化水平降低。这些发现表明，Hic-5的可能功能是FAK与局灶性粘连的募集，以及竞争性地抑制巴西林的酪氨酸磷酸化。
Hydrogen peroxide-inducible clone (Hic)-5 is induced during the senescent process in human fibroblasts, and the overexpression of Hic-5 induces a senescence-like phenotype. Structurally, Hic-5 and paxillin, a 68-kDa cytoskeletal protein, share homology such as the LD motifs in the N-terminal half and the LIM domains in the C-terminal half, Here we show that Hic-5 binds to focal adhesion kinase (FAR) by its N-terminal domain, and is localized to focal adhesions by its C-terminal LIM domains. However, Hic-5 is not tyrosine phosphorylated either by the coexpressed FAK in COS cells or by integrin stimulation in 293T cells. Furthermore, overexpression of Hic-5 results in a decreased tyrosine phosphorylation of paxillin. These findings suggest that putative functions of Hic-5 are the recruitment of FAK to focal adhesions and a competitive inhibition of tyrosine phosphorylation of paxillin.