Schreiber V, Moog-Lutz C, Régnier C H, Chenard M P, Boeuf H, Vonesch J L, Tomasetto C, Rio M C
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP Strasbourg, Illkirch, France.
Mol Med. 1998 Oct;4(10):675-87.
The Lasp-1 gene, which has been localized to the q12-q21 region of human chromosome 17, is amplified and overexpressed in human breast cancers. In addition to the previously reported LIM and SH3 domains of Lasp-1, we report here the identification of an actin-binding domain in the core of the protein. This domain is functional as we demonstrate that Lasp-1 binds actin in vivo and in vitro. In addition, confocal analysis of the Lasp-1 subcellular distribution shows that the protein is colocalized with actin at peripheral cell extensions in individual epithelial cancer cells and in transformed fibroblastic cells. Moreover, Lasp-1 is tyrosine phosphorylated in fibroblast cell lines transformed by a constitutively active form of c-Src (c-SrcY527F). Altogether, our results show that Lasp-1 defines a new type of actin-binding protein and suggest that the protein may play a role in a signaling pathway involved in the organization of the cytoskeleton.
Lasp-1基因定位于人类17号染色体的q12-q21区域，在人类乳腺癌中呈扩增及过表达状态。除了先前报道的Lasp-1的LIM和SH3结构域，我们在此报告在该蛋白核心区域鉴定出一个肌动蛋白结合结构域。该结构域具有功能，因为我们证明Lasp-1在体内和体外均能结合肌动蛋白。此外，对Lasp-1亚细胞分布的共聚焦分析表明，该蛋白在单个上皮癌细胞和转化的成纤维细胞的外周细胞延伸部位与肌动蛋白共定位。而且，在由组成型活性形式的c-Src（c-SrcY527F）转化的成纤维细胞系中，Lasp-1发生酪氨酸磷酸化。总之，我们的结果表明Lasp-1定义了一种新型的肌动蛋白结合蛋白，并提示该蛋白可能在参与细胞骨架组织的信号通路中发挥作用。
