Activator of G-protein signaling 3 (AGS3, encoded by GPSM1) was discovered as a one of several receptor-independent activators of G-protein signaling, which are postulated to provide a platform for divergence between canonical and noncanonical G-protein signaling pathways. Similarly, Dishevelled (DVL) proteins serve as a point of divergence for β-catenin-dependent and -independent signaling pathways involving the family of Frizzled (FZD) ligands and cell-surface WNT receptors. We recently discovered the apparent regulated localization of dishevelled-2 (DVL2) and AGS3 to distinct cellular puncta, suggesting that the two proteins interact as part of various cell signaling systems. To address this hypothesis, we asked the following questions: (1) do AGS3 signaling pathways influence the activation of β-catenin (CTNNB1)-regulated transcription through the WNT–Frizzled–Dishevelled axis, and (2) is the AGS3 and DVL2 interaction regulated? The interaction of AGS3 and DVL2 was regulated by protein phosphorylation, subcellular distribution, and a cell-surface G-protein-coupled receptor. These data, and the commonality of functional system impacts observed for AGS3 and DVL2, suggest that the AGS3–DVL2 complex presents an unexpected path for functional integration within the cell.

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G 蛋白信号传导激活剂 3（AGS3，由GPSM1编码）被发现是几种独立于受体的 G 蛋白信号传导激活剂之一，推测其为经典和非经典 G 蛋白信号传导途径之间的分歧提供了一个平台。同样，Disheveled (DVL) 蛋白是涉及卷曲 (FZD) 配体家族和细胞表面 WNT 受体的 β-连环蛋白依赖性和独立性信号通路的分歧点。我们最近发现dishevelled-2 (DVL2) 和AGS3 明显受调控地定位到不同的细胞斑点，这表明这两种蛋白作为各种细胞信号系统的一部分相互作用。为了解决这个假设，我们提出了以下问题：(1) AGS3 信号通路是否通过 WNT-Frizzled-Dishevelled 轴影响 β-catenin (CTNNB1) 调节转录的激活，以及 (2) AGS3 和 DVL2 相互作用监管？AGS3 和 DVL2 的相互作用受到蛋白质磷酸化、亚细胞分布和细胞表面 G 蛋白偶联受体的调节。这些数据以及观察到的 AGS3 和 DVL2 功能系统影响的共性表明，AGS3-DVL2 复合物为细胞内的功能整合提供了一条意想不到的途径。

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