Division of Bioengineering, Graduate School of Engineering Science, Osaka University, Toyonaka, Japan.
Cytoskeleton (Hoboken). 2021 Mar;78(3):67-76. doi: 10.1002/cm.21659. Epub 2021 Apr 7.
Rho-GTPase-activating proteins (Rho-GAPs) are essential upstream regulators of the Rho family of GTPases. Currently, it remains unclear if the phenotypic change caused by perturbations to a Rho-GAP is predictable from its amino acid sequence. Here we analyze the relationship between the morphological response of cells to the silencing of Rho-GAPs and their primary structure. For all possible pairs of 57 different Rho-GAPs expressed in MCF10A epithelial cells, the similarity in the Rho-GAP silencing-induced morphological change was quantified and compared to the similarity in the primary structure of the corresponding pairs. We found a distinct correlation between the morphological and sequence similarities in a specific group of RhoA-targeting Rho-GAPs. Thus, the family-wide analysis revealed a common feature shared by the specific Rho-GAPs.
Rho-GTPase 激活蛋白（Rho-GAPs）是 Rho 家族 GTP 酶的重要上游调节因子。目前，尚不清楚对 Rho-GAP 的干扰所引起的表型变化是否可以从其氨基酸序列中预测。在这里，我们分析了细胞对 Rho-GAP 沉默的形态反应与其一级结构之间的关系。对于 MCF10A 上皮细胞中表达的所有 57 种不同 Rho-GAP 的所有可能的成对组合，定量比较了 Rho-GAP 沉默诱导的形态变化的相似性与相应成对物的一级结构的相似性。我们发现，一组特定的靶向 RhoA 的 Rho-GAP 中的形态和序列相似性之间存在明显的相关性。因此，全家族分析揭示了特定 Rho-GAP 共有的一个共同特征。
