Matos Paulo, Jordan Peter
Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal.
Exp Cell Res. 2005 May 1;305(2):292-9. doi: 10.1016/j.yexcr.2004.12.029.
The small GTPase Rac1 can stimulate various signaling pathways following a tightly controlled GDP-GTP exchange. A splicing variant designated Rac1b was found to exist predominantly in the active GTP-bound state but the functional consequences of its expression remain unknown. Here we used mouse fibroblasts as a model to assess the signaling properties of Rac1b. We show that, in contrast to Rac1, expression of wild-type Rac1b is sufficient to stimulate cyclin D1 accumulation and G1/S progression in these cells. Moreover, expression of wild-type Rac1b, but not of wild-type Rac1, dramatically increased cell survival in the presence of only minimal growth stimuli. Both cellular responses were blocked by the NF-kappaB super-repressor IkappaBalpha(A32A36). Active Rac1b induced the phosphorylation and membrane translocation of IkappaBalpha, a prerequisite for the activation of NF-kappaB. These data demonstrate that Rac1b is a highly active Rac1 variant that stimulates cell cycle progression and cell survival in pathways involving NF-kappaB.
小GTP酶Rac1在严格控制的GDP-GTP交换后可刺激多种信号通路。一种名为Rac1b的剪接变体被发现主要以活性GTP结合状态存在，但其表达的功能后果仍不清楚。在这里，我们以小鼠成纤维细胞为模型来评估Rac1b的信号特性。我们发现，与Rac1相反，野生型Rac1b的表达足以刺激这些细胞中细胞周期蛋白D1的积累和G1/S期进程。此外，在仅存在最小生长刺激的情况下，野生型Rac1b而非野生型Rac1的表达显著提高了细胞存活率。这两种细胞反应均被NF-κB超级抑制剂IκBα（A32A36）阻断。活性Rac1b诱导IκBα的磷酸化和膜转位，这是NF-κB激活的先决条件。这些数据表明，Rac1b是一种高度活跃的Rac1变体，可在涉及NF-κB的通路中刺激细胞周期进程和细胞存活。
