Dutt Parmesh, Kjoller Lars, Giel Maryann, Hall Alan, Toksoz Deniz
Physiology Department, 136 Harrison Avenue, Tufts University School of Medicine, Boston, MA 02111, USA.
FEBS Lett. 2002 Nov 20;531(3):565-9. doi: 10.1016/s0014-5793(02)03625-6.
Rho GTPase is required for actin filament assembly and serum response element (SRE)-dependent gene transcription. Certain G protein-coupled receptors (GPCRs) induce Rho-dependent responses, but the intermediary signaling steps are poorly understood. The heterotrimeric Galpha12 family can induce Rho-dependent responses. In contrast, there are conflicting reports on the role of the Galphaq family in Rho signaling. We report that expression of activated Galphaq members, or activation of endogenous Galphaq via GPCR stimulation, induces SRE reporter activation via Rho, and increased GTP-Rho levels. Moreover, microinjection of activated Galphaq in fibroblasts induces actin stress fiber formation via Rho. Galphaq functionally cooperates with Lbc Rho guanine nucleotide exchange factor. Overall, these findings indicate that Galphaq family signals are sufficient to induce Rho-dependent cellular responses.
Rho GTP酶对于肌动蛋白丝组装和血清反应元件(SRE)依赖性基因转录是必需的。某些G蛋白偶联受体(GPCR)可诱导Rho依赖性反应,但中间信号传导步骤尚不清楚。异源三聚体Gα12家族可诱导Rho依赖性反应。相比之下,关于Gαq家族在Rho信号传导中的作用存在相互矛盾的报道。我们报告,活化的Gαq成员的表达,或通过GPCR刺激激活内源性Gαq,可通过Rho诱导SRE报告基因激活,并增加GTP-Rho水平。此外,在成纤维细胞中显微注射活化的Gαq可通过Rho诱导肌动蛋白应力纤维形成。Gαq与Lbc Rho鸟嘌呤核苷酸交换因子在功能上协同作用。总体而言,这些发现表明Gαq家族信号足以诱导Rho依赖性细胞反应。