Regulation of tensin-promoted cell migration by its focal adhesion binding and Src homology domain 2
Regulation of tensin-promoted cell migration by its focal adhesion binding and Src homology domain 2
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DOI：
10.1042/bj20021308
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发表时间：
2003-03-15
影响因子：
4.1
通讯作者：
Lo, SH
中科院分区：
文献类型：
--
作者：
Chen, HY;Lo, SH
Tensinl是一种肌动蛋白和磷酸酪氨酸结合蛋白，定位于局灶粘连。最近，我们发现tensin I和一个新的家族成员tensin2都能促进细胞迁移[Chen， Duncan, Bozorgchami and Lo (2002) Proc. Natl.]。学会科学。[美国文献99,733-738]。由于蛋白质在特定细胞内区室的定位经常调节其功能，并且Src同源结构域2可能介导与细胞迁移相关的信号，我们假设紧张素介导的细胞迁移是由局灶粘附定位和紧张素的Src同源结构域2调节的。为了验证这一假设，我们分析了一系列紧张素突变对细胞迁移的影响。我们的研究结果表明：(1)tensinl含有两个局灶黏附结合位点，(2)野生型tensini显著促进细胞迁移，(3)具有一个局灶黏附结合位点的突变体不促进细胞迁移，(4)非局灶黏附定位突变体抑制细胞迁移，(5)不能与含磷酸酪氨酸蛋白结合的突变体对细胞迁移没有影响。这些结果表明，张力蛋白的黏附定位和磷酸酪氨酸结合活性是调节张力蛋白介导的细胞迁移的两个关键因素。
Tensinl is an actin- and phosphotyrosine-binding protein that localizes to focal adhesions. Recently, we have shown that both tensin I and a new family member, tensin2, promote cell migration [Chen, Duncan, Bozorgchami and Lo (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 733-738]. Since localization of proteins to particular intracellular compartments often regulates their functions, and Src homology domain 2 may mediate signals related to cell migration, we hypothesize that tensin-mediated cell migration is regulated by the focal adhesion localization and the Src homology domain 2 of tensin. To test this hypothesis, we have analysed the effects of a series of tensin] mutants on cell migration. Our results have shown that (1) tensinl contains two focal adhesion-binding sites, (2) the wild-type tensin I significantly promotes cell migration, (3) mutants with one focal adhesion-binding site do not promote cell migration, (4) the non-focal adhesion localized mutant suppresses cell migration and (5) the mutant that is not able to bind to phosphotyrosine-containing proteins has no effect on cell migration. These results have indicated that focal adhesion localization of tensinl and the phosphotyrosine-binding activity are two critical factors in regulating tensin-mediated cell migration.