Identification of activator of G-protein signaling involved in cardiovascular disease

心血管疾病中 G 蛋白信号传导激活剂的鉴定

• 批准号: 18599006
• 负责人: SATO Motohiko
• 金额: $ 2.47万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18599006/
• 关键词: G-protein; Signal trasnduction; Cardiovascular disease

Recent data indicate the existence of signal regulators that directly influence the activation state of G-proteins independent of a GPCR. As part of a strategy to identify such entities involved in the development of cardiovascular disease, we utilized a functional screen in the yeast for the receptor-independent activators of heterotrimeric G-protein signaling and identified activators of G-protein signaling (AGS) 8 from rat heart following treatment of repetitive ischemia. We report here the extension of this approach to identify AGS involved in the development of cardiac hypertrophy. cDNA libraries were generated from hypertrophic heart of the mouse following treatment of isoproterenol (60 ug/g/day) or transverse aorta constriction for 7-9 days. The libraries were applied to the yeast system expressing Gsα or Giα3 as well as Gα16. Using the Giα3 yeast strain, we isolated cDNAs encoding AGS2 and 3 as well as RGS12. Using the Gα16 yeast strain, we isolated 3 candidates for novel AGS (novel-AGSs) representing 3 unique coding sequences belonged to the same functional group. The bioactivity of novel-AGSs was also observed in yeast strains expressing Gas, but not Gαi3. By interfacing to Gαl 6 or Gas signaling pathways, novel-AGSs may contribute to the development of cardiac hypertrophy.

最近的数据表明，存在的信号调节器，直接影响G-蛋白的激活状态的独立的GPCR。作为识别参与心血管疾病发展的此类实体的策略的一部分，我们在酵母中利用了异源三聚体G蛋白信号传导的受体非依赖性激活剂的功能筛选，并在反复缺血治疗后从大鼠心脏中识别了G蛋白信号传导的激活剂（AGS）8。我们在这里报告这种方法的扩展，以确定AGS参与心脏肥大的发展。在用异丙肾上腺素（60 μ g/g/天）或横主动脉收缩处理7-9天后，从小鼠的肥大心脏产生cDNA文库。将文库应用于表达Gsα或Giα3以及Gα16的酵母系统。使用Giα3酵母菌株，我们分离了编码AGS 2和3以及RGS 12的cDNA。利用Gα16酵母菌株，我们分离了3个新型AGS（novel-AGS）的候选者，代表3个属于相同功能组的独特编码序列。还在表达Gas但不表达Gαi3的酵母菌株中观察到新型AGSs的生物活性。通过介导Gα 16或Gas信号通路，新型AGSs可能有助于心肌肥大的发展。

项目成果

Caveolin improves glucose metabolism in diabetic mice

Caveolin 改善糖尿病小鼠的葡萄糖代谢

• 发表时间: 2007
• 作者: Koji Otsu;Jin Oshikawa;et. al.
• 通讯作者: et. al.

AGS3. UCSD-Nature Molecule Pages

AGS3。

• 发表时间: 2007
• 期刊: 10.1038, 000228.01
• 作者: Blumer,J;et. al.
• 通讯作者: et. al.

Rising Oxygen Tension Promoted Smooth Muscle Cell Migration in the Rat Ductus Arteriosus

氧张力升高促进大鼠动脉导管中平滑肌细胞迁移

• 发表时间: 2008
• 作者: Akaike T;et. al.
• 通讯作者: et. al.

Signaling by a non-dissociated complex of G-protein beta gamma and alpha subunits stimulated by a receptor-independent activator of G protein signaling, AGS8

由非解离的 G 蛋白 β γ 和 α 亚基复合物发出的信号，由 G 蛋白信号传导的受体独立激活剂 AGS8 刺激

• 发表时间: 2007
• 期刊: J Biol Chem 282
• 作者: Yuan;C;et. al.
• 通讯作者: et. al.

Characterization of activator of G protein signaling 8 in cardiomyocyte

心肌细胞中 G 蛋白信号传导激活剂 8 的表征

• 发表时间: 2008
• 作者: Honda;et. al.
• 通讯作者: et. al.