Gαq介导的信号通路增强RGS4蛋白表达

Gαq-Mediated Signaling Pathway Stimulates RGS4 Expression

RGS(regulators of G protein signaling)是G蛋白偶联信号通路中一类重要的调节蛋白,通过加速Gα结合的GTP水解,即GAP(GTPase activating protein)活性,来中止G蛋白信号通路。RGS4是RGS蛋白家族中的重要成员之一,它能有效中止Gαq介导的信号通路。作者研究了Gαq蛋白对RGS4蛋白的表达调控。当在HEK293细胞中共转染这两个蛋白时,持续性激活的Gαq能特异性地显著增加RGS4蛋白的表达。蛋白降解实验结果证明这种增强作用与RGS4的降解被抑制无关,而与RGS4 mRNA表达增强有关。进一步克隆RGS4蛋白的启动子区域并研究其与RGS4表达相互关系的实验结果又表明,持续性激活的Gαq能够显著增强RGS4启动子区的转录活性,且具有时间和浓度效应。同时,转录因子结合区突变体实验证明,ICE(inverted CCAAT box element)转录因子结合区的突变显著影响RGS4基因的转录活性。以上结果表明Gαq可能通过RGS4的启动子区调控其基因的表达,促进RGS4蛋白表达。

RGS （regulators of G protein signaling） proteins play an important role in regulation of G protein-coupled signaling transduction pathways. These proteins act as GTPase activating proteins （GAP） for heterotrimeric Gα subunits, thereby accelerating the termination of G protein-mediated signal transduction. RGS4, one of members of the RGS family, can selectively attenuate the intensity and duration of Gαq-mediated signal transduction. The authors investigated the regulation of RGS4 expression by Gαq-mediated signal transduction in this paper. When RGS4 and Gα were co-transfected in HEK293 cells, constitutively active Gαq but not other Gα subunits could specifically stimulate RGS4 protein expression. CHX-Chase assay and RT-PCR analysis showed that Go, q-mediated up-regulation of RGS4 protein is due to an increase of RGS4 mRNA synthesis but not inhibition of its degradation. They cloned the proximal promoter of RGS4, and found that constitutively active Gαq could significantly increase RGS4 promoter activity in a concentration- and time-dependent manner. Furthermore, using mutagenesis analysis, they demonstrated that the ICE transcription factor binding site was critical for RGS4 promoter activity. All together, these results suggest that Gαq-mediated signal transduction pathway stimulates RGS4 protein exDression via enhancement of RGS4 promoter activitv.