p130Cas couples the tyrosine kinase Bmx/Etk with regulation of the actin cytoskeleton and cell migration
p130Cas couples the tyrosine kinase Bmx/Etk with regulation of the actin cytoskeleton and cell migration
复制标题
DOI：
10.1074/jbc.m306438200
复制
发表时间：
2003-09-12
影响因子：
4.8
通讯作者：
Vuori, K
中科院分区：
文献类型：
--
作者：
Abassi, YA;Rehn, M;Vuori, K
BMX/ETK是Tec/BTK非受体激酶家族中的一员，最近被证明在整合素介导的细胞黏附激活的信号通路中调节细胞运动(Chen，R.，Kim，O.，Li，M.，Xong，X.，Guan，J.L.，Kung，H.J.，Chen，H.，Shimizu，Y.，and Chu，Y.(2001)NAT Cell Biol)。3,439-444)。到目前为止，BMX诱导细胞运动的分子机制尚不清楚。我们和其他人以前的研究已经证明，对接蛋白p130(Cas)(Cas)和适配蛋白Crk之间的复杂结构有助于将几种刺激连接到肌动蛋白细胞骨架和细胞运动的调节中。我们在这里证明了BMX的表达导致了BMX和膜皱纹上的CA之间的相互作用，这是运动细胞中活跃的肌动蛋白重塑的位置。BMX的表达也促进了Cas和Cas的酪氨酸磷酸化。CRK复合体的形成和BMX与Cas的共表达导致了细胞膜皱缩和向肝细胞迁移的增强。重要的是，突变形式的BMX不能与CA相互作用，也不能诱导细胞迁移。此外，不能与Crk相互作用的显性-负性形式的Cas的表达抑制了BMX诱导的膜褶皱和细胞迁移。这些研究表明，BMX-Cas相互作用，BMX对Cas的磷酸化，以及随后的Cas。CRK复合体的形成在功能上将BMX偶联到肌动蛋白细胞骨架和细胞运动的调节上。
Bmx/Etk, a member of the Tec/Btk family of nonreceptor kinases, has recently been shown to mediate cell motility in signaling pathways that become activated upon integrin-mediated cell adhesion ( Chen, R., Kim, O., Li, M., Xiong, X., Guan, J. L., Kung, H. J., Chen, H., Shimizu, Y., and Qiu, Y. ( 2001) Nat Cell Biol. 3, 439 - 444). The molecular mechanisms of Bmx-induced cell motility have so far remained unknown. Previous studies by us and others have demonstrated that a complex formation between the docking protein p130(Cas) (Cas) and the adapter protein Crk is instrumental in connecting several stimuli to the regulation of actin cytoskeleton and cell motility. We demonstrate here that expression of Bmx leads to an interaction between Bmx and Cas at membrane ruffles, which are sites of active actin remodeling in motile cells. Expression of Bmx also enhances tyrosine phosphorylation of Cas and Cas . Crk complex formation, and coexpression of Bmx with Cas results in an enhanced membrane ruffling and haptotactic cell migration. Importantly, a mutant form of Bmx that fails to interact with Cas also fails to induce cell migration. Furthermore, expression of a dominant-negative form of Cas that is incapable of interacting with Crk inhibits Bmx-induced membrane ruffling and cell migration. These studies suggest that Bmx-Cas interaction, phosphorylation of Cas by Bmx, and subsequent Cas . Crk complex formation functionally couple Bmx to the regulation of actin cytoskeleton and cell motility.