Characterization of novel activator of G protein signalings (AGSs) indentified in the hypertrophic heart.

在肥厚心脏中鉴定出的新型 G 蛋白信号传导 (AGS) 激活剂的表征。

• 批准号: 20590212
• 负责人: SATO Motohiko
• 金额: $ 3.16万
• 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: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590212/
• 关键词: 細胞内情報伝達; G蛋白質; 心肥大

In addition to G-protein coupled receptors, there exist receptor-independent regulators for heterotrimeric G-proteins which provide alternative signal input that may be involved in the adaptation process of cells to various stresses. As a part of an effort to identify such entities in cardiovascular diseases, we used a functional screen to identify receptor-independent activators of G-protein signaling (AGS) in the hypertrophied mouse heart by transverse aortic constriction. We identified three MITF/TFE transcription factors, TFE3 as novel AGS proteins for Gα16. TFE3 induced translocation of Gα16 to the nucleus. Interestingly, the accumulation of TFE3/Gα16 in the nucleus induced the expression of claudin 14, which was a key component of membrane structure in cardiomyocytes.TFE3 transcription factor is a new AGS for Gα16, that appears to generate a TEF3/Gα16 complex in the nucleus that drives the transcription of claudin 14. These findings suggest the existence of a novel mechanism of transcriptional regulation under pressure overload stress via the relocalization/activation of Gα subunit with specific AGS proteins.

除了G蛋白偶联受体之外，还存在异源三聚体G蛋白的受体非依赖性调节剂，其提供可能参与细胞对各种应激的适应过程的替代信号输入。作为鉴定心血管疾病中这些实体的努力的一部分，我们使用功能筛选来鉴定通过横向主动脉收缩的肥大小鼠心脏中的G蛋白信号传导（AGS）的受体非依赖性激活剂。我们鉴定了三个MITF/TFE转录因子，TFE 3是Gα16的新AGS蛋白。TFE 3诱导Gα16向细胞核转位。有趣的是，TFE 3/Gα16在细胞核中的积累诱导了claudin 14的表达，claudin 14是心肌细胞膜结构的关键组成部分，TFE 3转录因子是Gα16的一个新的AGS，它似乎在细胞核中产生TEF 3/Gα16复合物，驱动claudin 14的转录。这些结果表明，压力过载胁迫下存在一种新的转录调控机制，即通过特异性AGS蛋白对Gα亚基的重新定位/激活。

项目成果

PGE2-activated Epac promotes neointimal cushion formation of the rat ductus arteriosus by a process distinct from that of PKA.

PGE2 激活的 Epac 通过与 PKA 不同的过程促进大鼠动脉导管的新内膜垫形成。

• 发表时间: 2008
• 期刊: J Biol Chem. 1283(42)
• 作者: Yokoyama U;Minamisawa S (correspondence);Quan H;Akaike T;Suzuki S;Jin M;Jiao Q;Watanabe M;Otsu K;Iwasaki S;Nishimaki S;Sato M;Ishikawa Y.
• 通讯作者: Ishikawa Y.

Roles of Ischemia-Inducible G-protein activator, Activator of G-protein Signaling 8 : Regulation of Apoptosis and Connexin 43 of Cardiomyocytes.

缺血诱导 G 蛋白激活剂、G 蛋白信号传导激活剂 8 的作用：心肌细胞凋亡和连接蛋白 43 的调节。

• 发表时间: 2009
• 作者: 佐藤元彦;他3名
• 通讯作者: 他3名

Alterations of cardiac connexin 43 under hypoxic stress : roles of Activator of G protein Signaling 8 and Gbetagamma.

低氧应激下心脏连接蛋白 43 的变化：G 蛋白信号传导 8 激活剂和 Gbetagamma 的作用。

• 发表时间: 2009
• 作者: Jiao Q;et al
• 通讯作者: et al

Type 5 adenylyl cyclase plays a major role in stabilizing heart rate in response to microgravity induced by parabolic flight.

• DOI: 10.1152/japplphysiol.01166.2007
• 发表时间: 2008-07
• 期刊: Journal of applied physiology
• 影响因子: 3.3
• 作者: S. Okumura;T. Tsunematsu;Y. Bai;Q. Jiao;Shinji Ono;Sayaka Suzuki;R. Kurotani;Motohiko Sato;S. Minamisawa;S. Umemura;Y. Ishikawa

Regulation of Connexin43 by activator of G protein signaling 8 and Gbetagamma.

G 蛋白信号传导 8 和 Gbetagamma 激活剂对 Connexin43 的调节。

• 发表时间: 2010
• 作者: 佐藤元彦;他5名
• 通讯作者: 他5名