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.

中文翻译：

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统计分析揭示了细胞对 Rho-GAP 的反应与一级结构之间的相关性

Rho-GTPase 激活蛋白 (Rho-GAPs) 是 GTP 酶 Rho 家族的重要上游调节因子。目前，尚不清楚由扰动 Rho-GAP 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。对于在 MCF10A 上皮细胞中表达的 57 种不同 Rho-GAP 的所有可能对，量化了 Rho-GAP 沉默诱导的形态变化的相似性，并与相应对的一级结构的相似性进行了比较。我们发现一组特定的 RhoA 靶向 Rho-GAP 的形态学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 共有的共同特征。