PhYsiological function of focal adiesion protein vinexin

细胞迁移在各种生理和病理生理条件下发挥重要作用，包括伤口愈合、血管生成和肿瘤侵袭。阐明细胞迁移的机制有助于开发新的抗癌或抗转移药物。本研究利用vinexin基因敲除小鼠和敲减细胞研究了一种新的粘着斑蛋白vinexin在伤口愈合、细胞迁移和信号转导中的作用。1）伤口愈合-我们发现vinexin基因的破坏诱导皮肤损伤伤口愈合延迟。在培养的角质形成细胞中vinexin表达的敲低表明vinexin通过调节EGRR的活化和定位来调节伤口愈合。2）信号传导的锚定依赖性-检查了vinexin调节ERK的锚定非依赖性活化的机制。我们发现vinexin抑制ERK的失活。我们还发现，锚定依赖性调节ERK的激活依赖于失活过程的一部分。3）在细胞骨架和扩散的调节中的作用-在高侵袭性HT 1080细胞中vinexin表达的敲低表明，vinexin通过控制小G蛋白的激活在细胞扩散中发挥作用。我们还发现，vinexin直接与WAVE 2，小G蛋白的下游因子，并调节其磷酸化和量。

Cell migration play important roles in various physiological and pathophysiological conditions, including wound healing, angiogenesis, and tumor invasion. Clarifying the mechanisms of cell migration can contribute to the development of new anti-cancer or anti-metastasis drugs. This research has investigated the function of a novel focal adhesion protein, vinexin, in wound healings, cell migration, and signal transduction,using vinexin-knock out mice and knockdown cells.1) Wound healing-We found that gene disruption of vinexin induces the delayed wound healing of cutaneous injury. Knockdown of vinexin expression in cultured keratinocytes showed that vinexin regulate wound healing through regulating the activation and localization of EGRR2) Anchorage-dependence of signaling-Mechanisms of regulating anchorage-independent activation of ERK by vinexin was examined. We found that vinexin inhibits the inactivation of ERK. We also showed that anchorage-dependent regulation of ERK activation depends on the inactivation process in part.3) Roles in the regulation of cytoskeleton and spreading-Knockdown of vinexin expression in Highly invasive HT1080 cells showed that vinexin has roles in cell spreading through the control of a small G-protein activation. We also found that vinexin directly associates with WAVE2, a downstream factor of the small G protein, and regulates its phosphorylation and amount.