INSERM U624, Stress Cellulaire, Marseille F-13288, France.
Oncogene. 2010 Apr 29;29(17):2528-39. doi: 10.1038/onc.2010.1. Epub 2010 Feb 8.
Vav proteins are guanine nucleotide exchange factors for Rho GTPases that regulate cell adhesion, motility, spreading and proliferation in response to growth factor signalling. In this work, we show that Vav2 expression delayed epidermal growth factor receptor (EGFR) internalization and degradation, and enhanced EGFR, ERK and Akt phosphorylations. This effect of Vav2 on EGFR degradation is dependent on its guanine nucleotide exchange function. Knockdown of Vav2 in HeLa cells enhanced EGFR degradation and reduced cell proliferation. epidermal growth factor stimulation led to co-localization of Vav2 with EGFR and Rab5 in endosomes. We further show that the effect of Vav2 on EGFR stability is modulated by its interaction with two endosome-associated proteins and require RhoA function. Thus, in this work, we report for the first time that Vav2 can regulate growth factors receptor signalling by slowing receptor internalization and degradation through its interaction with endosome-associated proteins.
Vav 蛋白是 Rho GTPases 的鸟嘌呤核苷酸交换因子，可调节细胞黏附、运动、铺展和增殖，以响应生长因子信号。在这项工作中，我们表明 Vav2 的表达延迟了表皮生长因子受体 (EGFR) 的内化和降解，并增强了 EGFR、ERK 和 Akt 的磷酸化。Vav2 对 EGFR 降解的这种影响依赖于其鸟嘌呤核苷酸交换功能。在 HeLa 细胞中敲低 Vav2 会增强 EGFR 的降解并减少细胞增殖。表皮生长因子刺激导致 Vav2 与 EGFR 和内体中的 Rab5 共定位。我们进一步表明，Vav2 对 EGFR 稳定性的影响受其与两种内体相关蛋白相互作用的调节，并需要 RhoA 功能。因此，在这项工作中，我们首次报道 Vav2 可以通过与其内体相关蛋白相互作用来减缓受体内化和降解，从而调节生长因子受体信号。
