Thy-1 regulates fibroblast focal adhesions, cytoskeletal organization and migration through modulation of p190 RhoGAP and Rho GTPase activity
Thy-1 regulates fibroblast focal adhesions, cytoskeletal organization and migration through modulation of p190 RhoGAP and Rho GTPase activity
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DOI：
10.1016/j.yexcr.2004.01.026
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发表时间：
2004-05-01
影响因子：
3.7
通讯作者：
Hagood, JS
中科院分区：
文献类型：
--
作者：
Barker, TH;Grenett, HE;Hagood, JS
Thy-1是一种糖磷脂-莫西醇(GPI)连接的细胞表面糖蛋白，位于非凹陷的脂筏微域中，其确切的生物学作用仍然是个谜。有证据表明，Thy-1通过src家族蛋白激酶影响细胞内信号传递，并调节黏附和迁移事件，如胸腺细胞黏附和轴突延伸。根据细胞表面是否存在Thy-1分类的原代成纤维细胞表现出明显不同的形态，在细胞因子和生长因子的产生和反应方面也不同。目前尚不清楚Thy-1在多大程度上调节了这些差异。研究结果表明，Thy-1在调节Rho GTP酶活性方面发挥了新的作用，Rho GTP酶是细胞黏附和细胞骨架组织的关键调节因子。内源性或异源Thy-1的表达促进局部黏附和应力纤维的形成，其特征是Rho GTPase活性增加，并抑制迁移。免疫印迹结果显示，Thy-1基因的表达抑制了src家族蛋白酪氨酸激酶(SFK)的激活，导致p190 Rho GTP酶激活蛋白(GAP)的磷酸化水平降低。这导致了活性Rho的净增加，以及应力纤维和局灶性粘连的增加。因此，我们得出结论：Thy-1表面表达通过调节p190 RhoGAP和Rho GTP酶的活性来调节成纤维细胞的灶性黏附、细胞骨架的组织和迁移。(C)2004 Elsevier Inc.保留所有权利。
The precise biological role of Thy-1, a glycophosphatidyl-mositol (GPI)-linked cell surface glycoprotein in non-caveolar lipid raft microdomains, remains enigmatic. Evidence suggests that Thy-1 affects intracellular signaling through src-family protein kinases, and modulates adhesive and migratory events, such as thymocyte adhesion and neurite extension. Primary fibroblasts sorted based on presence or absence of cell surface Thy-1 display strikingly distinct morphologies and differ with respect to production of and response to cytokines and growth factors. It is unclear the extent to which Thy-1 mediates these differences. Findings reported here indicate a novel role for Thy-1 in regulating the activity of Rho GTPase, a critical regulator of cellular adhesion and cytoskeletal organization. Endogenous or heterologous Thy-1 expression promotes focal adhesion and stress fiber formation, characteristic of increased Rho GTPase activity, and inhibits migration. Immunoblotting following transfection of RFL6 fibroblasts with Thy-1 demonstrates that Thy-1 expression inhibits src-family protein tyrosine kinase (SFK) activation, resulting in decreased phosphorylation of p190 Rho GTPase-activating protein (GAP). This results in a net increase in active Rho, and increased stress fibers and focal adhesions. We therefore conclude that Thy-1 surface expression regulates fibroblast focal adhesions, cytoskeletal organization and migration by modulating the activity of p190 RhoGAP and Rho GTPase. (C) 2004 Elsevier Inc. All rights reserved.