Fujita H, Kamiguchi K, Cho D, Shibanuma M, Morimoto C, Tachibana K
Department of Cancer Immunology & AIDS, Dana-Faber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Biol Chem. 1998 Oct 9;273(41):26516-21. doi: 10.1074/jbc.273.41.26516.
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 (FAK) 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.
过氧化氢诱导克隆（Hic）-5在人成纤维细胞衰老过程中被诱导，Hic-5的过表达诱导出衰老样表型。在结构上，Hic-5与一种68 kDa的细胞骨架蛋白桩蛋白具有同源性，比如在N端的一半有LD基序，在C端的一半有LIM结构域。在此我们表明，Hic-5通过其N端结构域与粘着斑激酶（FAK）结合，并通过其C端LIM结构域定位于粘着斑。然而，Hic-5无论是在COS细胞中与共表达的FAK一起，还是在293T细胞中通过整合素刺激，都不会发生酪氨酸磷酸化。此外，Hic-5的过表达导致桩蛋白的酪氨酸磷酸化减少。这些发现表明，Hic-5的假定功能是将FAK招募到粘着斑以及对桩蛋白酪氨酸磷酸化的竞争性抑制。
