c-Cbl regulates migration of v-Abl-transformed NIH 3T3 fibroblasts via Rac1.
c-Cbl regulates migration of v-Abl-transformed NIH 3T3 fibroblasts via Rac1.
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DOI：
10.1016/j.yexcr.2005.03.010
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发表时间：
2005-07
影响因子：
3.7
通讯作者：
Anjali M Teckchandani;T. Panetti;A. Tsygankov
中科院分区：
文献类型：
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作者：
Anjali M Teckchandani;T. Panetti;A. Tsygankov
像细胞粘附和迁移这样的细胞事件涉及肌动蛋白细胞骨架的复杂重排。我们以前已经表明，多结构域衔接蛋白c-Cbl促进肌动蛋白细胞骨架重组，导致v-Abl转化的NIH 3 T3成纤维细胞的粘附。在这份报告中，我们证明了c-Cbl也增强了v-Abl转化的NIH 3 T3成纤维细胞的迁移。c-Cbl的这种作用取决于其酪氨酸磷酸化，特别是其Tyr-731的磷酸化，这是PI-3′激酶与c-Cbl结合所必需的。此外，我们证明c-Cbl对v-Abl转化的成纤维细胞迁移的影响是由活性PI-3′激酶和小的GT3激酶Rac 1介导的。我们的研究结果还表明，泛素连接酶活性的c-Cbl是必需的，而空间定位的c-Cbl伪足是不需要观察到的c-Cbl对细胞迁移的影响。
Cellular events like cell adhesion and migration involve complex rearrangements of the actin cytoskeleton. We have previously shown that the multidomain adaptor protein c-Cbl facilitates actin cytoskeletal reorganizations that result in the adhesion of v-Abl-transformed NIH 3T3 fibroblasts. In this report, we demonstrate that c-Cbl also enhances migration of v-Abl-transformed NIH 3T3 fibroblasts. This effect of c-Cbl depends on its tyrosine phosphorylation, specifically on phosphorylation of its Tyr-731, which is required for binding of PI-3′ kinase to c-Cbl. Furthermore, we demonstrate that the effect of c-Cbl on migration of v-Abl-transformed fibroblasts is mediated by active PI-3′ kinase and the small GTPase Rac1. Our results also indicate that ubiquitin ligase activity of c-Cbl is required, while spatial localization of c-Cbl to the pseudopodia is not required for the observed effects of c-Cbl on cell migration.