FAK potentiates Rac1 activation and localization to matrix adhesion sites:: A role for βPIX
FAK potentiates Rac1 activation and localization to matrix adhesion sites:: A role for βPIX
复制标题
DOI：
10.1091/mbc.e06-03-0207
复制
发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Romer, Lewis H.
中科院分区：
文献类型：
--
作者：
Chang, Fumin;Lemmon, Christopher A.;Romer, Lewis H.
FAK是一种胞质蛋白酪氨酸激酶，在细胞附着于细胞外基质时被激活并定位于粘着斑。FAK空细胞扩散不良，并表现出改变的局灶性粘附周转。Rac1是Rho家族GTPases的成员，其促进膜褶皱、前缘延伸和细胞铺展。我们研究了FAK空和FAK再表达成纤维细胞中Rac 1的激活和亚细胞定位。FAK reexpressers有一个更强大的模式Rac1激活后，细胞粘附到纤连蛋白比FAK空细胞。在FAK再表达者中观察到Rac 1易位至粘着斑，但在FAK缺失细胞中很少。组成型活性L61Rac 1和显性阴性N17Rac 1的实验表明，Rac 1的激活状态调节其定位到局灶性粘连。我们证明FAK酪氨酸磷酸化β PIX，从而增加其与Rac1的结合。此外，β PIX促进了活化的Rac1靶向粘着斑和细胞扩散的效率。这些数据表明FAK通过β PIX的酪氨酸磷酸化在Rac 1的活化和粘着斑易位中起作用。
FAK, a cytoplasmic protein tyrosine kinase, is activated and localized to focal adhesions upon cell attachment to extracellular matrix. FAK null cells spread poorly and exhibit altered focal adhesion turnover. Rac1 is a member of the Rho-family GTPases that promotes membrane ruffling, leading edge extension, and cell spreading. We investigated the activation and subcellular location of Rac1 in FAK null and FAK reexpressing fibroblasts. FAK reexpressers had a more robust pattern of Rac1 activation after cell adhesion to fibronectin than the FAK null cells. Translocation of Rac1 to focal adhesions was observed in FAK reexpressers, but seldom in FAK null cells. Experiments with constitutively active L61Rac1 and dominant negative N17Rac1 indicated that the activation state of Rac1 regulated its localization to focal adhesions. We demonstrated that FAK tyrosine-phosphorylated beta PIX and thereby increased its binding to Rac1. In addition, beta PIX facilitated the targeting of activated Rac1 to focal adhesions and the efficiency of cell spreading. These data indicate that FAK has a role in the activation and focal adhesion translocation of Rac1 through the tyrosine phosphorylation of beta PIX.